United States of America

Page 1 of 276

Confidence Building Measure Return covering 2011

Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction

Submitted to the United Nations on 9 July 2012

Page 2 of 276

Declaration form on Nothing to Declare or Nothing New to Declare for use in the information exchange

Year of last Nothing declaration if Measure Nothing to declare new to nothing new to declare declare

A, Part 1

A, Part 2 (i)

A, Part 2 (ii)

A, Part 2 (iii)

F  1997

Date: 9 July 2012

State Party to the Convention: United States of America

Date of ratification/accession to the Convention: 26 March 1975

National point of contact: Mr. Christopher Park, Department of State Page 3 of 276

9 July 2012

Report of the United States of America to the United Nations Department for Disarmament Affairs

Pursuant to the procedural modalities agreed upon in April 1987 at the "Ad Hoc Meeting of Scientific and Technical Experts for STATES Parties to the Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction," the United States of America submits the following information under Article V of the Convention: Confidence Building Measure A, Part 1 Exchange of data on research centres and laboratories pages 4-21 Confidence Building Measure A, Part 2 Exchanges of information on national biological defence research and development programmes (i) Declaration page 23 (ii) Description pages 24-57 (iii) Facilities pages 58-220

Confidence Building Measure B Exchange of information on outbreaks of infectious diseases and similar pages 221-233 occurrences caused by toxins Confidence Building Measure C Encouragement of publication of results and promotion of use of knowledge pages 234- 239

Confidence Building Measure E Declaration of legislature, regulations, and other measures pages 240- 247

Confidence Building Measure G Declaration of vaccine production facilities pages 248-258 Appendix A List of the Biological Select Agents and Toxins, and NIAID Category A, B and C pages 259-263 Priority Pathogens Appendix B Compiled list of biological agents and toxins used for biodefense research pages 264-276 Page 4 of 276

Form A, Part 1 (i)

BWC - Confidence Building Measure

Exchange of data on research centres and laboratories

United States of America

9 July 2012 Page 5 of 276

Form A, Part 1

Exchange of data on research centres and laboratories1

In accordance with the agreement at the Third Review Conference, later amended by the Seventh Review Conference, that States Parties provide data on "each facility, within their territory or under their jurisdiction or control anywhere, which has any maximum containment laboratories meeting those criteria for such maximum containment laboratories as specified in the latest edition of the WHO1 Laboratory Biosafety Manual and/or OIE2 Terrestrial Manual or other equivalent guidelines adopted by relevant international organisations, such as those designated as biosafety level 4 (BL4, BSL4 or P4) or equivalent standards.”

The United States is providing data on all facilities operating at biosafety level 4 during 2011. Data on BSL-4 facilities currently under construction will be included in future U.S. CBM submissions beginning with the submission covering the year each such facility becomes operational.

In previous submissions, the United States has provided data on the Plum Island Animal Disease Center (PIADC) in Form A, Part 1 (i) as well as Form A, Part 2 (iii) due to the facility's historical significance. Beginning with the present submission, comprehensive data on the PIADC will be found exclusively in Form A, Part 2 (iii).

1 World Health Organization 2 World Organization for Animal Health Page 6 of 276

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

National Biodefense Analysis and Countermeasures Center (NBACC)

Declared in accordance with Form A, Part 2 (iii)

2. Responsible public or private organization or company.

U.S. Department of Homeland Security Science & Technology Directorate operated by Battelle National Biodefense Institute LLC

3. Location and postal address.

8300 Research Plaza Fort Detrick, Maryland 21702 United States

Fort Detrick, MD

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Homeland Security (DHS)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 976 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

NBACC conducts studies to fill in information gaps to better understand current and future biological threats; to assess vulnerabilities; and to determine potential impacts to guide the development of countermeasures such as detectors, drugs, vaccines, and decontamination technologies. When needed, NBACC conducts experimental programs to better characterize the benefits and risks of changes in U.S. biodefense preparations. NBACC also develops bioforensic assays and provides operational forensic analysis to support the attribution of Page 7 of 276

biocrime and bioterrorism.

The types of agents registered for use at NBACC are BSL-2 toxins, BSL-2 gram positive and gram negative bacterial agents, BSL-2 viral agents, BSL-3 gram positive and gram negative bacterial agents, BSL-3 viral agents, and BSL-4 viral agents.

1 The containment units which are fixed patient treatment modules, integrated with laboratories, should be identified separately. 2 For facilities with maximum containment units participating in the national biological defence research and development programme, please fill in name of facility and mark "Declared in accordance with Form A, Part 2 (iii)". 3 In accordance with the 1983 WHO Laboratory Biosafety Manual, or equivalent. Page 8 of 276

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)

Declared in accordance with Form A, Part 2 (iii)

2. Responsible public or private organization or company.

U.S. Army Medical Research and Materiel Command

3. Location and postal address.

1425 Porter Street Fort Detrick Frederick, Maryland 21702-5011 United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Defense (DOD) - wholly

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 1186 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

USAMRIID conducts research to develop strategies, products, information, procedures and training programs for medical defense against biological warfare threats and infectious diseases. Medical products developed to protect military personnel against biological agents include vaccines, drugs, diagnostic capabilities and various medical management procedures.

Additional information can be found at:

http://www.usamriid.army.mil/

Page 9 of 276

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

CDC, Office of Infectious Diseases (OID)

Declared in accordance with Form A, Part 2 (iii)

2. Responsible public or private organization or company.

Centers for Disease Control and Prevention

3. Location and postal address.

1600 Clifton Road N.E. Atlanta, Georgia 30333

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

Centers for Disease Control and Prevention (CDC) Internal (Laboratory Directed Research and Development LDRD) U.S. Department of Health and Human Services (HHS)

U.S. Department of Homeland Security (DHS) U.S. Environmental Protection Agency (EPA)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 136 m2 BSL 4 Laboratory 271 m2

BSL 4 Laboratory 136 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

Activities include developing diagnostic assays for public health, conducting molecular and antigenic characterization of microorganism, determining pathogenicity and virulence of infectious agents, determining natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases. Biodefense activities include those with select agents (the select agents list is available at: http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html). Page 11 of 276

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

National Institutes of Health (NIH), NIAID-Rocky Mountain Laboratories

Declared in accordance with Form A, Part 2 (iii)

2. Responsible public or private organization or company.

National Institutes of Health U.S. Department of Health and Human Services

3. Location and postal address.

903 South 4th Street Hamilton, Montana 59840

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

U.S. Department of Health and Human Services (HHS)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 631 m2 Total

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

Research activities involving viruses, bacteria, rickettsiae, protozoa, and prions revolve around pathogenesis studies, vaccinology, and development of therapeutic agents and rapid diagnostic assays in support of the civilian biodefense program.

Additional information can be found at:

http://www.niaid.nih.gov/about/organization/dir/rml/pages/default.aspx

http://www.niaid.nih.gov/about/organization/dir/rml/pages/overview.aspx

Page 13 of 276

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

Galveston National Laboratory (GNL) Complex including Robert E. Shope Laboratory

2. Responsible public or private organization or company.

The University of Texas Medical Branch

3. Location and postal address.

301 University Blvd. Galveston, Texas 77555

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

Universities U.S. Department of Agriculture (USDA) Private Foundations Pharmaceutical Industry U.S. Department of Energy (DOE) U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS) National Institutes of Health (NIH)

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 186 m2 Shope laboratory BSL 4 Laboratory 1022 m2 GNL laboratory

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The mission of the Galveston National Laboratory is to assist the National Institute of Allergy and Infectious Diseases and the nation in the development of an improved means for the prevention, diagnosis and treatment of potentially life-threatening diseases caused by naturally emerging and purposefully disseminated infectious agents. To accomplish this goal GNL conducts multidisciplinary research into the causes, modes of transmission, and mechanisms of infectious diseases. Studies focus on a number of pathogens requiring BSL-4 Page 15 of 276

containment, primarily those that cause viral hemorrhagic fevers, as well as some zoonotic viruses requiring enhanced BSL-3 containment. Products likely to emerge from research and investigations within the GNL include novel diagnostic assays, improved therapeutics and treatment models, and preventative measures such as vaccines.

Additional information can be found at:

http://www.utmb.edu/gnl/

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

The Betty Slick and Lewis J. Moorman, Jr. Laboratory Complex, Department of Virology and Immunology

2. Responsible public or private organization or company.

Texas Biomedical Research Institute

3. Location and postal address.

P.O. Box 760549 San Antonio, Texas 78245-0549 United States

Note: As of February 1, 2011 the company name has changed from Southwest Foundation for Biomedical Research to Texas Biomedical Research Institute.

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

National Institutes of Health (NIH) U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS)

Private Sector Companies Private Donors

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 114 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The mission of the Laboratory is to develop vaccines and therapeutics against viral pathogens, and to determine how viruses replicate and spread. Scientists are studying new and emerging disease threats, possible bioterrorism agents, and as-yet uncharacterized

agents for biodefense. TXBiomed (formerly Southwest Foundation for Biomedical Research) has permits from the U.S. Department of Agriculture and the Centers for Disease Page 17 of 276

Control to work on Select Agents.

Additional information can be found at:

http://www.TXBiomed.org

Form A, Part 1 (i)

Exchange of data on research centres and laboratories1

1. Name(s) of facility2.

Viral Immunology Center - National B Virus Resource Laboratory

2. Responsible public or private organization or company.

Georgia State University

3. Location and postal address.

P. O. Box 4118 Atlanta, Georgia 30302-4118

United States

4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence.

National Institutes of Health (NIH) Georgia Research Alliance Immunology Core Support Elizabeth R. Griffin Research Foundation

5. Number of maximum containment units3 within the research centre and/or laboratory, with an indication of their respective size (m2).

BSL 4 Laboratory 60 m2

6. Scope and general description of activities, including type(s) of microorganisms and/or toxins as appropriate.

The Viral Immunology Center provides a global resource to assist in the identification of zoonotic disease transmissions and to develop enhanced strategies to detect viral infections in macaques. Current projects in the National B Virus Resource Laboratory are focused on the molecular biology of human and non-human primate alphaherpesviruses and the diseases they cause. Studies focus on the mechanisms by which virus kills the host and how that process can be circumvented with:

 Early identification - research focuses on the design and development of new approaches to more effectively identify these agents in both natural and foreign hosts;  Appropriate antiviral drugs - researchers continually screen the efficacy of Page 19 of 276

existing as well as novel antiviral agents to inhibit the growth of viruses that can potentially cross into the human population, either through occupational exposure or through more subtle contact; and  In the future, effective vaccines.

Additional information can be found at:

http://www2.gsu.edu/~wwwvir/Research/Index.html

Form A, Part 1 (ii)

BWC - Confidence Building Measure

Exchange of data on research centres and laboratories

United States of America

9 July 2012 Page 21 of 276

Form A, Part 1 (ii)

If no BSL4 facility is declared in Form A, Part 1 (i), indicate the highest biosafety level implemented in facilities handling biological agents4 on a State Party's territory:

Biosafety level 3 Yes5

Biosafety level 2 (if applicable) Yes6

4 Microorganisms pathogenic to humans and/or animals. 5 In accordance with the latest edition of the WHO Laboratory Biosafety Manual and/or the OIE Terrestrial Manual or other equivalent internationally accepted guidelines. 6 In accordance with the latest edition of the WHO Laboratory Biosafety Manual and/or the OIE Terrestrial Manual or other equivalent internationally accepted guidelines. Page 22 of 276

Form A, Part 2 (i)

BWC - Confidence Building Measure

National biological defence research and development programmes - Declaration

United States of America

9 July 2012

Page 23 of 276

National biological defence research and development programmes

Declaration

Are there any national programmes to conduct biological defence research and development within the territory of the State Party, under its jurisdiction or control anywhere? Activities of such programmes would include prophylaxis, studies on pathogenicity and virulence, diagnostic techniques, aerobiology, detection, treatment, toxinology, physical protection, decontamination and other related research.

Yes Page 24 of 276

Form A, Part 2 (ii)

BWC - Confidence Building Measure

National biological defence research and development programmes - Description

United States of America

9 July 2012 Page 25 of 276

Form A, Part 2 (ii)

National biological defence research and development programme

Description

The United States Government conducts a broad effort to reduce the risks presented by the deliberate or accidental release of biological agents and to defend against those threats in the event they occur. As called for by the National Strategy for Countering Biological Threats, this encompasses a range of initiatives, including improving global access to the life sciences to combat infectious disease regardless of its cause; establishing and reinforcing norms of safe and responsible conduct within the life sciences; improving capacity to detect and respond to outbreaks as they occur; and instituting a suite of coordinated activities that collectively help to influence, identify, inhibit, and/or interdict those who seek to misuse the life sciences.

One key element of this effort is the U.S. biodefense enterprise, which itself includes a variety of research and development programs aimed at protecting against the deliberate use of biological materials to cause harm. These programs focus on the identification of harmful pathogens and outbreaks of infectious diseases and their containment, treatment, and elimination from the environment. These programs are managed by several agencies with direct stakes in national security, environmental protection, and human and animal health and safety, including the Departments of Agriculture, Defense, Energy, Health and Human Services, Homeland Security, and the Environmental Protection Agency.

Historically, certain pathogens were selected for use as biological weapons because of their pathogenicity. Research on these pathogens, including study of molecular mechanisms and related diagnostic, vaccine and therapeutic development work, not only increases U.S. biodefense preparedness, but offers inherent benefits for broader public health needs. Efforts to improve medical product stability, potency and ease-of-use that cut across disease targets could yield significant benefits for public health systems that cannot support existing treatments that require refrigeration, multiple doses or sophisticated diagnostic techniques. Similarly, biodefense initiatives to improve human and animal host defenses, to monitor emerging infectious diseases and drug-resistant microbes, and to clean up the site of a biological weapons attack have civilian applications that benefit public health services, such as epidemiological disease surveillance and environmental remediation.

To promote the benefits gained by these programs and to ensure that the research is available to the scientific community both domestically and internationally, the United States Government encourages the publication of research funded by its biodefense programs.

For more information on U.S. Government strategies related to biodefense, including biological threat preparedness and response, please consult:

 Management of Domestic Incidents (Homeland Security Presidential Directive-5 [HSPD- 5]) and the related National Response Framework;  National Preparedness (HSPD-8); Page 26 of 276

 National Strategy for Defense of United States Agriculture and Food (HSPD-9);  National Biodefense Strategy (HSPD-10/National Security Presidential Directive-33 [NSPD-33]);  Medical Countermeasures against Weapons of Mass Destruction (HSPD-18);  Public Health and Medical Preparedness (HSPD-21); and:  National Strategy for Countering Biological Threats.

Web links to the Homeland Security Presidential Directives (HSPDS), issued by the President on matters pertaining to homeland security, can be found at: http://www.dhs.gov/xabout/laws/editorial_0607.shtm

The National Strategy for Countering Biological Threats can be found at: http://www.whitehouse.gov/sites/default/files/National_Strategy_for_Countering_BioThreats.pdf Page 27 of 276

Form A, Part 2 (ii)

National biological defence research and development programme

Description

The Chemical and Biological Defense Program (CBDP) provides support and world-class capabilities enabling the U.S. Armed Forces to fight and win decisively in chemical, biological, radiological, and nuclear (CBRN) environments. Established by Statute in 1994, the CBDP supports a comprehensive strategic framework to improve biological defense preparedness, reduce risk to the nation, and field the appropriate mix of capabilities for sustained military operations with minimum degradation of combat effectiveness attributed to current biological hazards and emerging threats.

The Program works to protect the nation from biological threats by providing medical countermeasure capabilities, building on current strengths but recognizing a changing environment. This includes an agile and flexible national capability and capacity to produce medical countermeasures rapidly to counter known or unknown threats, including novel and naturally occurring emerging infectious diseases. Current research focuses on a recombinant botulinum vaccine, a recombinant vaccine for protection against pneumonic plague, test and evaluation of medical countermeasures against biological threat/terrorism agents, and the advanced development and licensure of other vaccines and biological products designed to protect against a variety of biological agents. Page 28 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

1. State the objectives and funding of each programme and summarize the principal research and development activities conducted in the programme. Areas to be addressed shall include: prophylaxis, studies on pathogenicity and virulence, diagnostic techniques, aerobiology, detection, treatment, toxinology, physical protection, decontamination and other related research.

Joint Biological Point Detection System. Produce and field a fully automated system for point sampling, detecting, and identifying biological agents in an aerosolized environment. Develop, produce and field subsystems to reduce detection false positives and lower ownership costs.

Joint Biological Tactical Detection System. Develop, produce and field a man-portable

family of systems for point sampling, detecting, and identifying biological agents in an aerosolized environment.

Joint Biological Stand-off Detection System. Develop, produce and field a system for detecting biological agent clouds at certain stand-off distances.

2. State the total funding for each programme and its source.

$100,836,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

59 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

1) Produce components and systems 2) Develop and test new sensor hardware and software components

3) Develop system test methods

6. Provide a diagram of the organizational structure of each programme and the Page 29 of 276

reporting relationships (include individual facilities participating in the programme).

7. Provide a declaration in accordance with Form A, Part 2 (iii) for each facility, both governmental and non-governmental, which has a substantial proportion of its resources devoted to each national biological defence research and development programme, within the territory of the reporting State, or under its jurisdiction or control anywhere.

Not Applicable

Page 30 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The program objective is to identify or prepare and characterize "reactive materials" to produce self-disinfecting and/or self-decontaminating materials for incorporation into protective gear and other materiel in order to provide personnel and equipment protection against both environmental and weaponized pathogens.

2. State the total funding for each programme and its source.

$1,444,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

40 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

To classify the particle size distribution of bioaerosols, building precision aerosol deposition devices and studying post-capture fate of iodine on bioaerosol particles.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 31 of 276

In accordance with Form A part 2 (iii): • Tyndall AFB -- 1

• Tyndall AFB -- 2

Page 32 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

In recent years global surveillance networks have determined that the frequency and diversity with which new infectious microorganisms are emerging is increasing. While these increases are in part due to improved reporting, multiple examples demonstrate this increase is promulgated by changes in natural systems, and potentially the activities of humans. One growing concern is the potential risk posed by the proliferation of powerful, global available genetic engineering technologies that can be easily redirected from beneficent to offensive purposes or for covert biological industrial-scale sabotage of the agricultural sector. Together, these natural occurring and unnaturally occurring synthetic threat agents challenge

both current detection methods and current medical countermeasures.

The goal of the 7-Day Biodefense program is to develop innovative approaches to counter any pathogen. The program comprises four specific technical areas investigating novel technologies to: (1) Prevent Infection; (2) Sustain Survival; (3) Provide Transient Immunity; and (4) Create Persistent Immunity. Methods being explored do not require prior knowledge of the pathogen and are broadly applicable to multiple unrelated infectious agents.

2. State the total funding for each programme and its source.

$36,179,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

99.34 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4. Page 33 of 276

7-Day Biodefense is developing identity-agnostic countermeasures effective against any pathogen. It addresses the unknown, as pathogen identification is not required. The program saves years on isolation, attenuation, cultivation and animal models and if successful will provide technologies to confer and maintain protection against any pathogen (natural or synthetic) within 7 Days. By assuming the initial and highest risk for R&D in the drug development cycle, 7-Day Biodefense will dramatically reduce barriers to follow-on candidates from both traditional and emerging pharmaceutical companies and academic discovery programs.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

Not Applicable

Page 34 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

To develop and acquire Food and Drug Administration approved vaccines and biologics to be used as biological defense medical countermeasures.

2. State the total funding for each programme and its source.

$87,879,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

71 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Includes advanced development of candidates for medical countermeasures to include: preclinical safety and efficacy studies, process development, assay validation, clinical/non- clinical studies, pilot lot production, manufacturing scale-up, validation, demonstration, and consistency lot manufacturing, Phase 2 clinical trials, and pivotal animal efficacy studies.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 35 of 276

Not Applicable

Page 36 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

Emerging Infectious Diseases Flu countermeasure (EID-Flu): To protect the service member from an ineffective vaccine, a naturally occurring endemic or biologically engineered

influenza virus.

2. State the total funding for each programme and its source.

$307,300,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

90 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Conduct Food and Drug Administration clinical trials

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 37 of 276

Not Applicable

Page 38 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The Hemorrhagic Fever Virus (HFV) Medical Countermeasures (MCM) Acquisition Program provides the capability to ameliorate the effects of HFV exposure. The design concept is to develop a Food and Drug Administration (FDA)-licensed MCM based on broad spectrum platform technologies. The selected platform will initially develop FDA- approved MCMs against members of the lethal Filoviridae family (Ebola and Marburg

viruses) for which currently there are no vaccines or treatments available. The program is designed to provide incremental capabilities and as such is being developed to create a platform technology that allows for the development of MCMs against multiple HFV agents individually.

2. State the total funding for each programme and its source.

$373,900,000 U.S. Department of Defense (DOD)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

80 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Develop FDA approved Medical Countermeasures/Therapeutics against Ebola and Marburg viruses based on platform drug technologies.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 39 of 276

Not Applicable

Page 40 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The Environmental Protection Agency (EPA)'s mission is to protect public health and the environment. The National Homeland Security Research Center (NHSRC), part of the EPA's Office of Research and Development, conducts and reports on research to improve capacity to respond to and recover from environmental contamination of water infrastructure, buildings and outdoor areas by chemical, biological, radiological and nuclear (CBRN) agents. The NHSRC biodefense program focuses on EPA's two biodefense responsibilities: 1) assistance in the protection of the American water supply, and 2) decontamination of indoor and outdoor areas should the U.S. suffer a contamination incident.

EPA is designated as the government's lead sector-specific agency for water, and is responsible for protecting water systems and detecting and recovering from terrorist attacks affecting them. EPA's homeland security research is responsible for developing products and providing expertise to protect, detect, respond to, and recover from terrorist attacks on the nation's water and wastewater infrastructure.

EPA is also the lead federal agency for the remediation of areas contaminated by terrorist events involving the release of biological organisms, biotoxins, chemical warfare agents, toxic industrial chemicals, toxic industrial materials, and radiological materials. Terrorist acts may involve biological, chemical, and radiological agents not previously encountered as environmental pollutants. EPA's homeland security research is responsible for providing procedures and methods that will assist EPA's responders in the detection and containment of contamination, and in the remediation of sites following terrorist attacks.

2. State the total funding for each programme and its source.

$7,800,000 U.S. Environmental Protection Agency (EPA)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these Page 41 of 276

contracted or other facilities?

31 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

NHSRC has research being conducted by contractors to assess risks of biological agents. Animal exposure studies are being conducted to estimate doses that result in adverse health effects from biological hazards. To address the need for remediating contaminated sites,

NHSRC has been evaluating as well as developing analytical methods for detecting and remediating biological agents.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

Not Applicable

Page 42 of 276

Form A, Part 2 (ii)

National biological defence research and development programme

Description

Overview of HHS Biodefense Programs and Activities

The U.S. Department of Health and Human Services (HHS) is the lead Federal agency for ensuring the health of civilian populations by, among other things, preventing, preparing for, and responding to the adverse health effects of public health emergencies and disasters. HHS biodefense programs support inter alia public health preparedness, biosurveillance capabilities, and research aimed at developing medical products and strategies to diagnose, treat and prevent a wide range of infectious diseases, whether those diseases emerge naturally or are deliberately introduced as a malicious act (criminal or terrorist). HHS also has a key role in implementing the Biological Weapons Convention (BWC) tenets and the United Nations Security Council Resolution 1540 (UNSCR 1540) through its legal authority conferred inter alia by the Public Health Service Act of 1944 as amended; Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1962 as amended; the Antiterrorism & Effective Death Penalty Act of 1996; Uniting & Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001 (USA PATRIOT Act); Public Health Security & Bioterrorism Preparedness and Response Act of 2002; Pandemic and All-Hazards Preparedness Act (PAHPA) of 2006 and the Food and Drug Administration (FDA) Food Safety Modernization Act of 2011. In accordance to its mandate, HHS leads many programs and initiatives aimed at biological risk management and biodefense (including the Select Agents Regulations and associated program, The Foreign Quarantine Regulations/ Interstate Transportation of Etiologic Agents and the associated Etiologic Agent Import Permit Program, as well as Food Defense Programs).

Below is a list of select operating and staff divisions of HHS involved in biodefense activities. For complete list of HHS staff and operating divisions, please see: http://www.hhs.gov/open/contracts/index.html#od.

Office of the Assistant Secretary for Preparedness and Response (ASPR) (ASPR website: http://www.PHE.gov)

On behalf of the HHS Secretary, the Assistant Secretary for Preparedness and Response (ASPR) leads the Federal public health and medical response to public health emergencies and incidents covered by the National Response Framework and provides leadership in international programs, initiatives, and policies that relate to public health and medical emergency preparedness and response. ASPR is the HHS Secretary's principal advisor on matters related to Federal public health and medical preparedness and response to public health emergencies. ASPR is the primary HHS liaison to the U.S. Department of State and National Security Staff on Biological Weapons Convention (BWC), United Nations Security Council Resolution 1540 (UNSCR 1540), and the G8 Global Partnership Against the Spread of Weapons and Materials of Mass Destruction, and leads the HHS coordination of related policy initiatives. ASPR provides leadership in the Page 43 of 276 development and implementation of policies, plans and initiatives relevant to the WHO International Health Regulations (2005) (IHR) and facilitates implementation and manages/operates the HHS Secretary's Operation Center (SOC), which is the IHR National Focal Point. ASPR serves as a Global Health Security Action Group (GHSAG) Senior Official for HHS. GHSAG implements the Global Health Security Initiative (GHSI) - an international partnership created to strengthen global health preparedness and response for the threats of biological, chemical, radiological-nuclear terrorism (CBRN) and pandemic influenza.

Within ASPR, the Office of Policy and Planning (OPP) advises HHS and ASPR leadership on policy options and strategic planning to support domestic and international public health emergency preparedness and response activities within ASPR, HHS, and the Federal Government. OPP serves as the focal point for the National Security Staff (NSS) policy coordination activities on behalf of ASPR and leads the development and implementation of an integrated ASPR approach to policy. On behalf of HHS, ASPR is supporting the U.S. Department of State in its public diplomacy demarches related to the Biological Weapons Convention (BWC), represents HHS in the U.S. delegation to the BWC and coordinates the HHS reporting on CBMs. In collaboration with the U.S. Department of Defense, ASPR organized in 2011 an international workshop and tabletop exercise aimed at establishing regional and international partnerships to strengthen the core capacities required by the WHO IHRs and existing national measures consistent with the obligations under the BWC and UNSCR 1540 to deter, prevent, and respond to biological incidents or threats (Countering Biological Threats: National Implementation of the Biological Weapons Convention and Multinational Outbreak Response and Bioterrorism Investigation Demonstration, Tbilisi, Georgia, 17-19 May 2011; workshop report is available online at: http:www.phe.gov/Preparedness/international/Pages/counteringthreats.aspx).

Through the Office of Policy and Planning, ASPR is developing policy and operational frameworks for the deployment and exchange of medical countermeasures and medical personnel for international public health emergencies. Simultaneously, ASPR is looking at the issues related to receiving international assistance in the case of a significant domestic disaster, addressing issues of licensure, privileging and liability. In addition, ASPR manages the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE). PHEMCE is a coordinated interagency effort which is responsible for: defining and prioritizing requirements for public health emergency medical countermeasures; focusing research, development, and procurement activities on the identified requirements; and establishing deployment and use strategies for medical countermeasures in the Strategic National Stockpile.

An organizational element within the ASPR Office, the Biomedical Advanced Research and Development Authority (BARDA) provides an integrated, systematic approach to the development and purchase of the necessary vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies. BARDA manages Project BioShield, which includes the procurement and advanced development of medical countermeasures for chemical, biological, radiological, and nuclear agents. BARDA also is engaged in the advanced development and procurement of medical countermeasures for pandemic influenza and other emerging infectious diseases that fall outside the auspices of Project BioShield. More information on BARDA is available at: http://www.phe.gov/about/barda/Page/default.aspx. Page 44 of 276

The ASPR's Strategic Plan for 2011-2015 is available online at: http:www.phe.gov/about/aspr/strategic-plan/Pages/default.aspx.

Office of Global Affairs (OGA) (OGA website: http://globalhealth.gov/)

The Office of Global Affairs (OGA) is part of the HHS Office of the Secretary. OGA promotes the health of the world's population by advancing HHS's global strategies and partnerships and working with U.S. Government agencies in the coordination of global health policy, security and initiatives. OGA is the lead coordinating Office in global health and other international affairs for HHS. It performs these duties for the HHS Secretary and for the HHS Operating and Staff Divisions (OPDIVS / StaffDIVS). OGA's mission is to provide policy advice and direction to the Secretary, Deputy Secretary, and other HHS senior officials. OGA provides advice and direction in the areas of international health, family, and social affairs, including health diplomacy in support of U.S. foreign policy. OGA has the opportunity and responsibility to contribute greatly to the U.S. global health enterprise and other foreign affairs priorities of our country. To accomplish this mission, OGA is organized around an international relations division. It has regional branches, a program coordination division, and a strategy and policy division. The international relations division has health attachés in six countries and personnel on the U.S. - México border. As an example of recent bilateral engagement, within the structure of the Health Working Group of the U.S.-Russia Bilateral Presidential Commission, on 27 January 2011, the US Department of Health and Human Services, the Ministry of Health and Social Development of the Russian Federation, and the United States Agency for International Development (USAID), signed in Geneva a Protocol of Intent on Cooperation for the Global Eradication of Polio. The participants intend to work jointly and in collaboration with other partners, as may be further arranged, in areas that may include: providing technical assistance for polio surveillance; participating in and monitoring of polio immunization campaigns; providing technical assistance on polio clinical diagnosis, case management and rehabilitation; advocacy and resource mobilization; and such additional areas as may be mutually decided upon by the Participants.

The Centers for Disease Control and Prevention (CDC)

The Centers for Disease Control and Prevention's (CDC) programs provide countermeasures to be used to protect the U.S. civilian population through research and development for vaccines and therapeutic agents and rapid, agent-specific assays. The CDC also provides information and resources for preparing for and responding to public health emergencies. Additional information is available at: http://emergency.cdc.gov/. CDC's strategic plan for biodefense is based on the following five focus areas, with each area integrating training and research:

 preparedness and prevention;  detection and surveillance;  diagnosis and characterization of biological and chemical agents;  response; and  communication. Page 45 of 276

The Homeland Security Presidential Directive 21 (HSPD-21) charged the Department of Health and Human Services (HHS) with the responsibility of enhancing biosurveillance for human health and HHS delegated this responsibility to CDC. The National Biosurveillance Strategy for Human Health (NBSHH) was released in February 2010 (available online at: http://cdc.gov/osels/pdf/NBSHH v2/.pdf ). The Concept Plan for Implementation of the National Biosurveillance Strategy for Human Health was released in January 2010 (http://www.cdc.gov/osels/pdf/Fact%20Sheet%Governance.pdf)). The CDC's Public Health Surveillance Program Office, Biosurveillance Coordination (BC) unit also provides support to the National Biosurveillance Advisory Subcommittee (NBAS), a HSPD-21 mandated independent advisory committee comprised of prominent public and private biosurveillance stakeholders and contributors. In June 2011, BC published its second report on "Improving the Nation's Ability to Detect and Respond to 21st Century Urgent Health Threats: Second Report of the National Biosurveillance Advisory Subcommittee" (available online at: http://www.cdc.gov/osels/pdf/NBAS Final Report 2011.pdf ) which moved towards more specific recommended action steps to enhance our nation's biosurveillance capability.

CDC is also the lead agency for the HHS Select Agents Program. The registration of facilities and personnel possessing, using and transferring these agents or toxins is part of the government's efforts to improve the ability of the United States to prevent, prepare for, and respond to bioterrorism and other public health emergencies and is required under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. For more information about the Select Agents Program, please see the website of the National Select Agent Registry at: http://www.selectagents.gov.

Within the Office of Infectious Disease (OID), the national center for Emerging and Zoonotic Infectious Diseases (NCEZID) and the National Center for Immunization and Respiratory Diseases (NCIRD), located in Atlanta, Georgia, conduct a variety of activities, including diagnostic techniques, assay development, molecular and antigenic characterization of microorganisms, evaluation of decontamination methods, pathogenicity, virulence, natural history, and vaccine development for select agents. The select agents list is available at: http:selectagents.gov/Select%20Agents%20and%20Toxins%20List.html.

Within NCEZID, the Division of Vector-borne Diseases (DVBD), located in Fort Collins, Colorado, focuses on development and implementation of epidemiology and surveillance, prevention and control and improved diagnostics for diagnosis, detection and characterization of several vector-borne pathogens including various bacteria and alphaviruses, as well as serving as the national reference laboratory for these pathogens.

In addition, as a part of the CDC's National Center for Environmental Health, the Mass Spectrometry Toxin Laboratory is developing toxin assays that are critical for the public health response to biological toxins. The laboratory uses advanced mass spectrometry techniques to measure peptides and proteins that are in the pathogenic pathway of the infectious agent or toxin and uses these measurements to identify and track infection or poisoning.

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The Food and Drug Administration (FDA)

The U.S. Food and Drug Administration (FDA) leads U.S. Government efforts to ensure access to safe and effective human and veterinary drugs, biological products (including allergenics, blood products, cell therapy, plasma derivatives, tissue engineering and vaccines), medical and radiation-emitting devices, cosmetics, and a safe and nutritious food supply. As a part of this mission, the FDA works with other Government agencies and private sector organizations to help reduce the risk of tampering or other malicious, criminal, or terrorist actions on the food and cosmetic supply. The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Bioterrorism Act) has four key provisions to ensure the safety and security of food; it added § 801(l) to the Federal Food, Drug and Cosmetic (FD&C) Act, which provides that if an article of food being imported or offered for import is from a facility for which registration has not been submitted as required by § 415 of the FD&C Act, the article is subject to hold until the registration violation is corrected. The authority for carrying out these functions has been delegated by HHS Secretary to FDA. FDA also leads programs and initiatives on Food Defense and Emergency Response (which includes the Strategic Partnership Program- Agroterrorism, a joint effort of the FBI, DHS, USDA, and FDA). More information is available at: http:www.fda.gov/Food/FoodDefense/default.htm and http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048251.htm.

The National Institutes of Health (NIH)

The NIH, specifically the National Institute of Allergy and Infectious Diseases (NIAID), has the primary responsibility within the United States Government for civilian biodefense research. NIAID conducts and supports much of the research aimed at developing new and improved medical countermeasures against potential bioterrorism agents. The NIH/NIAID Strategic Plan for Biodefense Research is available online at: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/biosp2007.pdf. More information is also available at: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Pages/default.aspx.

NIAID labs involved in biodefense research include the Dale and Betty Bumpers Vaccine Research Center, IRF-Rocky Mountain Laboratories, and the C.W. Bill Young Center for Biodefense and Emerging Infectious Diseases.

In addition, the NIAID Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases (RCEs) support research focused on countering threats from bioterror agents and emerging infectious diseases. Each Center is comprised of a consortium of universities and research institutions serving a specific geographical region. The Centers, located throughout the United States, will build and maintain a strong scientific infrastructure supporting multifaceted research and development activities that promote scientific discovery and translational research capacity required to create the next generation of therapeutics, vaccines, and diagnostics. NIAID has set research priorities and goals for each microorganism that might be used as an agent of bioterrorism, with particular emphasis on "Category A" agents-those considered by the Centers for Disease Control and Prevention to be the most serious bioterror threats. NIAID's research agenda and strategic plan cover the following categories: Page 47 of 276

 Basic biology: understanding how microorganisms and/or their toxic products function and cause disease.  Immunology and host response: understanding how the human immune system interacts with and defends the body against potential agents of bioterrorism.  Vaccines: working closely with industry to create new and improved vaccines.  Drugs: working closely with industry to develop and test drugs to treat diseases that may result from a biological attack.  Diagnostics: developing devices or methods to quickly and accurately diagnose diseases caused by bioterrorism agents.  Research resources: establishing biosafety laboratories, databases, and other resources to help scientists conduct safe and effective biodefense research.

Additional information is available at: http://www.niaid.nih.gov/labsandresources/resources/rce/Pages/default.aspx.

The NIH Office of Biotechnology Activities (OBA) promotes science, safety, and ethics in biotechnology through advancement of knowledge, enhancement of public understanding, and development of sound public policies. OBA accomplishes its mission through analysis, deliberation, and communication of scientific, medical, ethical, legal, and social issues. NIH OBA manages the National Science Advisory Board for Biosecurity (NSABB), which advises the federal government on strategies to oversee research that may generate information, products, or technologies that could be misused to threaten public health or national security. NSABB is composed of 25 non-government subject matter experts as well as ex officio members from certain federal departments and agencies. The NSABB's purposes include: informing development of federal and institutional oversight guidelines and promoting awareness in the research community about the dual use issue; and fostering international collaboration on issues related to dual use research. The NSABB has produced six influential reports on a range of topics within the area of dual use research as well as educational materials which are freely available online and have been distributed at the BWC meetings during the 2007-2010 intersessional process (for more information see: http://oba.od.nih.gov/biosecurity/about_nsabb.html).

Ensuring safety and security in storing and handling infectious agents and toxins is a prerequisite for any life science activity and for keeping the trust of the public and that of decision makers. Such safeguarding is also an international obligation under the Biological Weapons Convention and the United Nations Security Council Resolution 1540 which require national legislation and other measures to prohibit and prevent the proliferation of biological weapons and the misuse of science and technology. NIH is also leading the National Biosafety and Biocontainment Training Program (NBBTP) which provides: i) Professional Certificate Programs for Biosafety and Biocontainment (B&B) professionals as well as for Operations and Maintenance (O&M) personnel working in high containment facilities; ii) Professional Development Courses (on the 2 tracks: B&B and O&M; distance learning and on-site); and iii) NBBTP Fellowships (post baccalaureate and postdoctoral) of 2-year professional training in biosafety and biocontainment at immersing tomorrow's biocontainment laboratory leadership in biosafety and biosecurity coursework, applied research, and experiential learning assignments. For more information, see: http://www.nbbtp.org. Page 48 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

Improving our nation's defenses against bioterrorism is a key part of the U.S. Government's homeland security effort. The Department of Health and Human Services (HHS) supports activities to improve local and state public health systems, to expand existing biosurveillance efforts, and to fund research on medical countermeasures against potential bioterror agents.

The National Institutes of Health (NIH) biodefense program is supported by funding from the U.S. Department of Health and Human Services. The NIH, and specifically the National Institute of Allergy and Infectious Diseases (NIAID), has the primary responsibility within the U.S. Government for civilian biodefense research. The intent of the program is to provide countermeasures to be used to protect the U.S. civilian population through the development of vaccines, therapeutic agents and rapid, agent-specific assays.

2. State the total funding for each programme and its source.

$61,943,720 U.S. Department of Health and Human Services (HHS)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

Not Applicable

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Not Applicable

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 49 of 276

In accordance with Form A part 2 (iii): National Institutes of Health (NIH), C.W. Bill Young Center for Biodefense and • Emerging Infectious Diseases

• National Institutes of Health (NIH), Dale and Betty Bumpers Vaccine Research Center • Integrated Research Facility (IRF) - Rocky Mountain Laboratories (RML)

Page 50 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The objective of the Mass Spectrometry Toxin Laboratory within CDC's National Center for Environmental Health, Division of Laboratory Sciences is to develop toxin assays that are critical for better detection and diagnosis during a public health response to biological toxins.

2. State the total funding for each programme and its source.

$1,893,766 Centers for Disease Control and Prevention (CDC)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

40 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

University of California at San Francisco: Synthesis of monoclonal antibodies for botulinum neurotoxin. Batelle Memorial Institute: Provides laboratory personnel to perform research and test clinical samples for the presence of botulinum neurotoxins and ricin

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme).

See next page.

7. Provide a declaration in accordance with Form A, Part 2 (iii) for each facility, both Page 51 of 276 governmental and non-governmental, which has a substantial proportion of its resources devoted to each national biological defence research and development programme, within the territory of the reporting State, or under its jurisdiction or control anywhere.

In accordance with Form A part 2 (iii): CDC, National Center for Environmental Health (NCEH), Division of Laboratory • Sciences (DLS)

Page 52 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

The activities of the CDC Office of Infectious Disease (OID) include developing diagnostic assays for public health, conducting molecular and antigenic characterization of microorganisms, evaluating decontamination methods, determining pathogenicity and virulence of infectious agents, determining the natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases. Biodefense activities include those with select agents. OID includes the National Center for Emerging Zoonotic Infectious

Diseases (NCEZID) and the National Center for Immunization and Respiratory Diseases (NCIRD).

The select agents list is available at: http://www.selectagents.gov/Select%20Agents%20and%20Toxins%20List.html

2. State the total funding for each programme and its source.

$22,449,223 Centers for Disease Control and Prevention (CDC)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

Yes

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

5 %

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Vaccine efficacy trials, reagent development, bioterrorism preparedness and response activities, avian influenza preparedness, and disease surveillance in CDC field locations.

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 53 of 276

In accordance with Form A part 2 (iii): CDC, OID, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), • Division of Vector Borne Diseases (DVBD) - Ft. Collins • CDC, Office of Infectious Diseases (OID)

Page 54 of 276

Form A, Part 2 (ii)

National biological defence research and development programmes

Description

U.S. Department of Agriculture (USDA)

Background

Foreign animal diseases represent a major threat to U.S. agriculture. Introduction of these agents, either accidental or deliberate, has devastating social and economic effects not only in the country's agricultural systems but also in a wide range of economic activities. Diseases of concern include but are not limited to Foot-and-Mouth Disease, Avian Influenza, Rift Valley Fever, Classical Swine Fever, African Swine Fever, Exotic Newcastle disease, Vesicular stomatitis, and Exotic Bluetongue.

Animal health officials define an exotic or foreign animal disease (FAD) as an important transmissible livestock or poultry disease believed to be absent from the U.S. and its territories that has a potential significant health or economic impact. Foreign animal diseases are considered a threat to the U.S. when they significantly affect human health or animal production and when there is an appreciable cost associated with disease control and eradication efforts. To protect the long-term health and profitability of U.S. animal agriculture, incursions of a FAD must be rapidly controlled.

In the U.S., control usually means disease eradication. Disease eradication is currently accomplished by eliminating the animal, resulting in loss of protein, loss of income to the farm community, public opposition and environmental disruption. In addition to control costs, one of the most immediate and severe consequences of a FAD occurrence in the U.S. will be the loss of export markets. Many new issues and factors are affecting FAD prevention, control, management, and recovery. These factors include free trade agreements, free trade blocks, regionalization, increased international passenger travel, intensification of animal production, the constant evolution of infectious agents, and the uncertain impact of biotechnology and bioterrorism.

Current methods for prevention and control of high consequence diseases, including prevention, detection, control and eradication, are not socially or economically acceptable. Rapid detection and characterization tools for prevention, control and eradication of foreign Page 55 of 276

animal diseases are inadequate or not currently available. Our understanding of pathogenesis, transmission, and immune response is insufficient to rapidly control and eradicate foreign animal diseases. Effective measures to prevent, control and eradicate foreign animal diseases are lacking or inadequate.

Strategic Objectives

 Establish Agriculture Research Service (ARS) laboratories into a fluid, highly effective research network, to maximize use of core competencies and resources.  Access to specialized high containment facilities to study zoonotic and emerging diseases.  Develop an integrated animal and microbial genomics research program.  Establish centers of excellence in animal immunology.  Launch a biotherapeutic discovery program providing alternatives to animal drugs.  Build a technology-driven vaccine and diagnostic discovery research program.  Develop core competencies in field epidemiology and predictive biology.  Develop internationally recognized OIE expert collaborative research laboratories.  Establish best in class training center for our nation's veterinarians and scientists.  Develop a model technology transfer program to achieve the full impact of our research discoveries.

Research Needs

In order to control foreign animal disease, a wide variety of agent detection platforms need to be developed and validated. Information for design of these platforms will come in part from further knowledge of pathogen genomics and proteomics and in part from understanding the evolution and genetic variability of disease agents. Although many of the foreign animal diseases have existed for many years in other countries, more fundamental knowledge of these agents is required. There is still a lack of understanding in host range and tissue tropism, carrier state, duration and routes of shedding, transmission mechanisms, (e.g., vectors, fomites, aerosols), ecology and epidemiology (e.g., wildlife reservoirs). If these diseases should occur in the U.S., more effective prevention and control tools, such as identifying suitable control strategies compatible with short time and cost of recovery from disease outbreaks (DIVA compatible), need to be developed. There is a need for development of vaccines and biotherapeutics suitable for strategic stockpiles and integrated methods of disease control, including vector control and animal management, which all lead to a better capability to regain country disease-free status and retain economic sustainability.

Expected Outputs:

 Better anticipation of introduction of foreign animal diseases.  Capability to advise regulatory officials on scientific procedures for the prevention of introduction of FADs.  Better capability to produce effective products to control and eliminate foreign Page 56 of 276

animal diseases.  Real-time detection of agents in a wide range of farm matrices.  Searchable databases of genome and proteome information for major known FAD agents.  Improved ability to predict or anticipate emergence or introduction of FAD agents.  Discovery of effective candidate biotherapeutics.  Discovery of effective candidate vaccines that allow differentiation of infected animals from vaccinated animals (DIVA).  Viable integrated vector control strategies that minimize losses.

The USDA-ARS biodefense research program is intramural and implemented in ARS high containment facilities in the following locations: Ames, Iowa; Orient Point, New York; Athens, Georgia; Frederick, Maryland.

2. State the total funding for each programme and its source.

$17,017,000 U.S. Department of Agriculture (USDA)

3. Are aspects of these programmes conducted under contract with industry, academic institutions, or in other non-defence facilities?

4. If yes, what proportion of the total funds for each programme is expended in these contracted or other facilities?

Not Applicable

5. Summarize the objectives and research areas of each programme performed by contractors and in other facilities with the funds identified under paragraph 4.

Not Applicable

6. Provide a diagram of the organizational structure of each programme and the reporting relationships (include individual facilities participating in the programme). Page 57 of 276

In accordance with Form A part 2 (iii): • Foreign Disease-Weed Science Research Unit • Plum Island Animal Disease Center (PIADC)

• Southeast Poultry Research Laboratory • National Animal Disease Center (NADC)

Page 58 of 276

Form A, Part 2 (iii)

BWC - Confidence Building Measure

National biological defence research and development programmes - Facilities

United States of America

9 July 2012 Page 59 of 276

Form A, Part 2 (iii)

National biological defence research and development programme

The U.S. Government identified potential concerns associated with public release of information on the identity of biological agents at specific facilities.

To balance these concerns with a desire to promote transparency, in Form A Part 2(iii) the U.S. submission characterizes the agents used for biological defense research at each facility by identifying:

 whether there are Biological Select Agent and Toxins (Select Agent) present at the facility, and if so, which subcategories (HHS, Overlap, USDA, and USDA PPQ) are represented;  for each Select Agent subcategory, whether these agents are also listed under NIAID Category A, B, or C Priority Pathogens;  whether there are non-Select Agent NIAID Category A, B or C Priority Pathogens present at the facility; and  other relevant information as appropriate

Biological Select Agents and Toxins (Select Agents) are biological agents or toxins that have the potential to pose a severe threat to public, animal or plant health, or to animal or plant products, whose possession, use and transfer are regulated by the Select Agent Rules. Additional information on Select Agents can be found at: http://www.selectagents.gov

The NIAID list of Category A, B and C Priority Pathogens identifies specific pathogens as priorities for additional research efforts as part of the NIAID biodefense research agenda.

Additional information on NIAID Category A, B and C Priority Pathogens can be found at: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Pages/CatA.aspx http://pathema.jcvi.org/pathema/AbcGenomes.shtml http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/categorybandc.pdf

Using the two lists to categorize the agents at a facility offers greater transparency into the types of agents than using either list alone. Lists of Biological Select Agents and Toxins, and NIAID Category A, B, C Priority Pathogens can be found in the Appendix of the CBM submission (pages 260-264). A compiled list of microorganisms and toxins used for biological defense research at the facilities reported in Form A Part 2(iii) can be found in Appendix B of the CBM submission (pages 265-271).

To maintain our existing high level of transparency to States Parties, we are making available, to all States Parties, information on agents consistent with previous submissions.

Page 60 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Biodefense Analysis and Countermeasures Center (NBACC)

2. Where is it located (provide both address and geographical location)?

8300 Research Plaza Fort Detrick, Maryland 21702

3. Floor area of laboratory areas by containment level:

BL2 1032 (sqM) BL3 3160 (sqM) BL4 976 (sqM) Total laboratory floor area 5168 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 151

(ii) Division of personnel:

Military 0

Civilian 151

(iii) Division of personnel by category:

Scientists 26

Engineers 30

Technicians 53

Administrative and support staff 42

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology Biochemistry Bioinformatics Biology Biomedical Science Biophysics Page 61 of 276

Biotechnology Cell Biology Chemistry Computer Science Genetics Immunology Molecular Biology Molecular Pathogenic Microbiology Veterinary Medicine Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 151

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Homeland Security (DHS)

(vii) What are the funding levels for the following program areas: Research $ 5,298,607 Development $ 8,339,428 Test and evaluation $ 0 Total $ 13,638,035

(viii) Briefly describe the publication policy of the facility: The NBACC publication policy is to present research results to the greater scientific community as widely as possible. As a Federally Funded Research and Development Center engaged in research with select agents/regulated pathogens, NBACC has established a formal, multi-tiered review system to ensure compliance and conformance with U.S. Government regulations including export control regulations under EAR/ITAR, the Biological Weapons Convention (BWC), and internal U.S. Department of Homeland Security (DHS) policies. All publications are reviewed by NBACC and DHS prior to release to ensure clarity and accuracy with regard to the description of the work.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Burtnick, M.N., Brett, P.J., Harding, S.V., Ngugu, S., Ribot, W.J., Chantratita, N., Scorpio, Page 62 of 276

A., Milne, T. S., Dean, R., Fritz, D. L., Peacock, S.J., Prior, J.L., Atkins, T.P., DeShazer, D. The Cluster 1 Type VI Secretion System is a Major Virulence Determinant in Burkholderia pseudomallei , (U). PLoS Pathogens Journal, Infect Immun. 2011 Apr;79(4):1512-25. Epub 2011 Feb 7.

Fitch, J.P., National Biodefense Analysis and Countermeasures Center. Encyclopedia of Bioterrorism Defense , 2nd Edition; Edited by Rebecca Katz and Raymond Zilinskas. June 2011; 420-429.

Goff, A.J., Chapman, J., Foster, C., Wlazlowski, C., Shamblin, J., Lin, K., Kreiselmeier, N., Mucker, E., Paragas, J., Lawler, J., and Hensley, L. A Novel Respiratory Model of Infection with Monkeypox Virus in Cynomolgus Macaques. Journal of Virology; May 2011; 85: 4898- 4909.

Ondov, B., Bergman, N.H., Phillippy, A.M. Interactive visualization of hierarchal information for metagenomics; BMC Bioinformatics. 2011 Sept 30, 12(1):385.

Salzberg SL, Phillippy AM, Zimin AV, Puiu D, Magoc T, Koren S, Treangen T, Schatz MC, Delcher AL, Roberts M, Marcais G, Pop M, Yorke JA. GAGE: A critical evaluation of genome assemblies and assembly algorithms . Genome Res. 2011. Dec 6.

Schatz, Michael C., Phillippy, A., Sommer, D., Delcher, A., Puiu, D., Narzisi, G., Salzberg, S., Pop, M. Hawkeye & AMOS: Visualizing and assessing the quality of genome assemblies. Briefings in Bioinformatics. 2011. Dec 23.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The NBACC mission is to provide the nation with the scientific basis for characterization of biological threats and bioforensic analysis to support attribution of their use against the American public. NBACC conducts studies to fill in information gaps to better understand current and future biological threats; to assess vulnerabilities; and to determine potential impacts to guide the development of countermeasures such as detectors, drugs, vaccines, and decontamination technologies. When needed, NBACC conducts experimental programs to better characterize the benefits and risks of changes in U.S. biodefense preparations. NBACC also develops bioforensic assays and provides operational forensic analysis to support the attribution of planned and actual events of biocrime and bioterrorism.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Page 63 of 276

Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 64 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Plum Island Animal Disease Center (PIADC)

2. Where is it located (provide both address and geographical location)?

40550 Rte. 25 Orient Point, New York 11957

3. Floor area of laboratory areas by containment level:

BL2 234 (sqM) BL3 17643 (sqM) BL4 0 (sqM) Total laboratory floor area 17877 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 357

(ii) Division of personnel:

Military 0

Civilian 357

(iii) Division of personnel by category:

Scientists 92

Engineers 2

Technicians 13

Administrative and support staff 250

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology Chemistry Engineering Microbiology Molecular Biology Molecular Computational Biology Page 65 of 276

Pathology Research Facility Operations Veterinary Medicine

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 250

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA) U.S. Department of Homeland Security (DHS)

(vii) What are the funding levels for the following program areas: Research $ 3,800,000 Development $ 8,000,000 Test and evaluation $ 4,000,000 Total $ 16,000,000

(viii) Briefly describe the publication policy of the facility: DHS scientific research staff is expected to publish papers in open literature. Papers are peer reviewed and approved by DHS prior to submittal to journals. USDA ARS has several publication policies (website links in parenthesis): Policy Number 150.1 "Dissemination of Public Information by ARS"

(http://www.afm.ars.usda.gov/ppweb/PDF/150-01.pdf); Number 113.1 "Publishing (Print and Electronic) (www.afm.ars.usda.gov/ppweb/2010/113-1-ARS.pdf); and Number 152.1 "Procedures for Publishing Manuscripts and Abstracts with Non-USDA Publishers (Outside Publishing) (http://www.afm.ars.usda.gov/ppweb/pdf/152-01.pdf)

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

2011 PIADC Publications Page 66 of 276

FADDL Publications in 2011

1. Barrette RW, Xu L, Rowland JM,McIntoshMT: 2011, Current perspectives on the phylogeny of Filoviridae. Infection, Genetics and Evolution, 11:1514-1519. 2. Das A, Beckham TR andMcIntoshMT: 2011, Comparison of methods for improved RNA extraction from blood for early detection of Classical swine fever virus by real- time reverse transcription polymerase chain reaction. Journal of Veterinary Diagnostic Investigation, 23:727-736. 3. De Wit E, Munster VJ, Metwally SA, Feldmann H: 2011, Assessment of rodents as animal models forRestonebolavirus. Journal of Infectious Diseases, Suppl 3:968- 972. 4. Eberling AJ, Bieker-Stefanelli J, Reising MM, Siev D, Martin BM, McIntosh MT, and Beckham TR: 2011, Development, optimization, and validation of a Classical swine fever virus real-time reverse transcription polymerase chain reaction assay. Journal of Veterinary Diagnostic Investigation, 23: 994-998. 5. Fernandez, JP and White WR: 2011, Atlas of Transboundary Animal Diseases, World Organization for Animal Health. 6. Mohamed F, Swafford S, Petrowski H, Bracht A, Schmit B, Fabian A, Pacheco JM, Hartwig E, Berninger M, Carrillo C, Mayr G, Moran K, Kavanaugh D, Leibrecht H, White W and Metwally S: 2011, Foot-and-mouth disease in feral swine: susceptibility and transmission. Transboundary and Emerging Diseases, 58: 358-371. 7. Rowland, JM, Rowland RRR, Geisbert T: 2011, Chapter 14, Ebolaviruses. Diseases of Swine (in press).

DHS Publications in 2011

1. Fernandez-Sainz I, Holinka LG, Gladue D, O'Donnell V, Lu Z, Gavrilov BK, Risatti GR, Borca MV: 2011, Substitution of specific cystine residues in the El glycoprotein of classical swine fever virus strain Brescia affects formation of E1-E2 heterodimers and alters virulence in swine. J Virol, 2011 Jul; 85(14) : 7264-72. 2. Gladue D, Holinka LG, Fernandez-Sainz I, Prarat MV, O'Donnell V, Vepkhvadze NG, Lu Z, Risatti GR, Borca MV: 2011, Interaction between Core protein of classical swine fever virus with cellular IQGAP1 protein appears essential for virulence in swine. Virology, 2011 Mar 30;412 (1) : 68-74.

ARS Publications in 2011

1. Piccone, M.E., Diaz-San Segundo, F., Kramer, E., Rodriguez, L.L., De LosSantos, T.B. 2011. Introduction of tag epitopes in the inter-AUG region of foot and mouth disease virus: effect on the L protein. Virus Research. 155(1):91-97. 2. Patch, J.R., Pederesen, L.E., Moraes, M.P., Grubman, M.J., Nielsen, M., Buus, S., Golde, W.T. 2011. Induction of foot-and-mouth disease virus specific cytotoxic T cell killing by vaccination. Clinical and Vaccine Immunology. 18(2):280-288. 3. Arroyo, M., Perez, A.M., Rodriguez, L.L. 2011. Characterization of the temporal and spatial distribution and reproductive ration of vesicular stomatitis outbreaks Page 67 of 276

inMexicoin 2008. American Journal of Veterinary Research. 2011(72):233-238. 4. O'Donnell, V., Pacheco Tobin, J., Larocco, M.A., Burrage, T., Jackson, W., Rodriguez, L.L., Borca, M.V., Baxt, B. 2011. Foot-and-mouth disease virus utilizes an autophagic pathway during viral replication. Virology. 410:142-150. 5. Dias, C.C., Moraes, M.P., Diaz-San Segundo, F., De LosSantos, T.B., Grubman, M.J. 2011. Porcine type I interferon rapidly protects swine against challenge with multiple serotypes of foot-and-mouth disease virus. Journal of Interferon and Cytokine Research. 31(2):227-236. 6. Gladue, D.P., Gavrilov, B.K., Holinka-Patterson, L.G., Fernandez-Sainz, I.J., Vepkhvadze, N.G.,Rogers, K., O'Donnell, V., Borca, M.V. 2011. Identification of an NTPase motif in classical swine fever virus NS4B protein. Virology. 411(1):41-49. 7. Rodriguez, L.L., Gay, C.G. 2011. Development of vaccines toward the global control and eradication of foot-and-mouth disease. Expert Review of Vaccines. 10(3):377-387. 8. Gladue, D.P., Holinka-Patterson, L.G., Fernandez-Sainz,I., Prarat, M.V., O'Donnell, V.K., Vepkhvadze, N., Lu, Z., Risatti, G.R., Borca, M.V. 2011. Interaction between core protein of classical swine fever virus with cellular IQGAP1 proetin appears essential for virulence in swine. Virology. 412:68-74. 9. Blignaut, B., Visser, N., Theron, J., Rieder, A.E., Maree, F.F. 2011. Custom- engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs. Journal of General Virology. 92(4):849-859. 10. Toka, F.N., Kenney, M.A., Golde, W.T. 2011. Rapid and transient activation of gamma/delta T cells to interferon gamma production, NK cell-like killing and antigen processing during acute virus infection. Journal of Immunology. 186(8):4853-4861. 11. Reis, J.L., Rodriguez, L.L., Mead, D.G., Smoliga, G.R., Brown, C.C. 2011. Lesion development and replication kinetics during early infection in cattle inoculated with vesicular stomatitisNew Jerseyvirus via scarification and black fly (Simulium vittatum) bite. Veterinary Pathology. 48(3):547-557. 12. Diaz-San Segundo, F., Weiss, M., Perez-Martin, E., Koster, M.J., Zhu, J.J., Grubman, M.J., De LosSantos, T.B. 2011. Antiviral activity of bovine type III interferon against foot-and-mouth disease virus. Virology. 413(2):283-292. 13. Fernandez-Sainz, I.J., Holinka-Patterson, L.G., Gladue, D.P., O'Donnell, V., Lu, Z., Gavrilov, B.K., Risatti, G.R., Borca, M.V. 2011. Substitution of specific cysteine residues in E1 glycoprotein of classical swine fever virus strainBresciaaffects formation of E1-E2 heterodimers and alters virulence in swine. Journal of Virology. 407:129-136. 14. Krug, P.W., Lee, L.J., Eslami, A.C., Larson, C.R., Rodriguez, L.L. 2011. Chemical disinfection of high-consequence transboundary animal disease viruses on nonporous surfaces. Biologicals. 39(4):231-235. 15. Golde, W.T., De LosSantos, T.B., Robinson, L., Grubman, M.J., Sevilla, N., Summerfield, A. 2011. Evidence of activation and suppression during the early immune response to foot-and-mouth disease virus. Transboundary and Emerging Diseases. 58(4):283-290. 16. Arzt, J., Juleff, N., Zhang, Z., Rodriguez, L.L. 2011. The pathogenesis of foot-and- Page 68 of 276

mouth disease I; viral pathways in cattle. Transboundary and Emerging Diseases. 58(4):291-304. 17. Arzt, J., Baxt, B., Grubman, M.J.,Jackson, T., Juleff, N., Rhyan, J., Rieder, A.E., Waters, R., Rodriguez, L.L. 2011. The pathogenesis of foot-and-mouth disease II; viral pathways in swine, small ruminants, and wildlife, myotropism, chronic syndromes, and molecular virus-host interactions. Transboundary and Emerging Diseases. 58(4):305-326. 18. Brito, B.P., Perez, A.M., Konig, G.A., Cosentino, B., Rodriguez, L.L. 2011. Factors associated with within-herd transmission of serotype A foot-and-mouth disease virus during the 2001 outbreak inArgentina: a protective effect of vaccination. Transboundary and Emerging Diseases. 58(5):387-93 19. Maree, F.F., Blignaut, B., Esterhuysen, J.J., De Beer, T., Theron, J., O'Neill, H.G., Rieder, A.E. 2011. Predicting antigenic sites on the foot-and-mouth disease virus capsid of theSouthAfricanTerritories(SAT) types using virus neutralization data. Journal of General Virology. 92(10):2297-2309 20. Maree, F.F., Blignaut, B., De Beer, T.A., Visser, N., Rieder, A.E. 2011. Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses. Virus Research. 153(1):82-91. 21. Gavrilov, B.K.,Rogers, K., Fernandez Sainz, I.J., Holinka-Patterson, L.G., Borca, M.V., Risatti, G.R. 2011. Effects of glycosylation on antigenicity and immunogenicity of classical swine fever virus envelope proteins. Virology. 420:135- 145. 22. Pauszek, S.J., Barrera, J.C., Goldberg, T., Allende, R., Rodriguez, L.L. 2011. Genetic and antigenic relationships of veicular stomatitis viruses fromSouth America. Archives of Virology. 156(11):1961-8 23. Barrette, R.W., Rood, D., Challa, S., Szczepanek, S.M., Avery, N., Vajdy, M., Kramer, E., Rodriguez, L.L., Silbart, L.K. 2011. Use of inactivated E.Coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine. Clinical and Vaccine Immunology. 18(11):1996-8 24. Moraes, M.P., Diaz San Segundo, F.C., Dias, C.C., Pena, L., Grubman, M.J. 2011. Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response. Vaccine. 29(51):9431-9440. 25. Pedersen, L.E., Harndahl, M.N., Rasmussen, M., Lamberth, K., Golde, W.T., Lund, O., Nielsen, M., Buus, S. 2011. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities. Immunogenetics. 63(12):821-34

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: PIADC provides the only research and development and confirmatory diagnostic capability Page 69 of 276

for specific high-consequence, contagious, foreign animal diseases of livestock, including foot-and-mouth disease, in theU.S. Technologies researched and developed are vaccines, antivirals and diagnostic methods.

(ii) Agents Microorganisms and/or Toxins:

• USDA Select Agents and Toxins • Other pathogens or toxins

(iii) Outdoor Studies: None

Page 70 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lothar Salomon Test Facility (LSTF)

2. Where is it located (provide both address and geographical location)?

2029 Burns Rd Dugway, Utah 84022-5006

3. Floor area of laboratory areas by containment level:

BL2 744 (sqM) BL3 414 (sqM) BL4 0 (sqM) Total laboratory floor area 1158 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 60

(ii) Division of personnel:

Military 0

Civilian 60

(iii) Division of personnel by category:

Scientists 43

Engineers 1

Technicians 6

Administrative and support staff 10

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology Bacteriology Biochemistry Engineering Immunology Microbiology Page 71 of 276

Molecular Biology Toxicology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 15

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) – partly U.S. Department of Justice (DOJ) U.S. Department of Homeland Security (DHS)

(vii) What are the funding levels for the following program areas: Research $ 231,000 Development $ 0 Test and evaluation $ 4,100,000 Total $ 4,331,000

(viii) Briefly describe the publication policy of the facility: Professional scientists are encouraged to publish papers in peer-reviewed journals. All publications must obtain the necessary command permission before submission.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Cheryl Fairfield Estill, Paul A. Baron, Jeremy K. Beard, Misty J. Hein, Lloyd D. Larsen, Gregory J. Deye, Laura Rose, and Lisa Hodges. Comparison of Air Sampling Methods for Aerosolized Spores of B. anthracis Sterne. February 2011. Journal of Occupational and Environmental Hygiene, 8: 179-186.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Testing of battlefield detection and identification methods, protective equipment, and

decontamination systems, to include interferent testing of biological detectors and to Page 72 of 276

develop/validate aerosol particle dispersion models.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: Yes - using simulants

Page 73 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Medical Research Center (NMRC)

2. Where is it located (provide both address and geographical location)?

503 Robert Grant Avenue Silver Spring, Maryland 20910

3. Floor area of laboratory areas by containment level:

BL2 100 (sqM) BL3 35 (sqM) BL4 0 (sqM) Total laboratory floor area 135 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 73

(ii) Division of personnel:

Military 12

Civilian 61

(iii) Division of personnel by category:

Scientists 16

Engineers 0

Technicians 50

Administrative and support staff 7

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry Immunology Microbiology Molecular Biology

(v) Are contractor staff working in the facility? If so, provide an approximate Page 74 of 276

number.

Yes Number: 56

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 2,999,280 Development $ 0 Test and evaluation $ 0 Total $ 2,999,280

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Brenneman KE, Dognanay M, Akmal A, Goldman S, Galloway DR, Mateczun AJ, Cross AS, Baillie LW. 2011. The early humoral immune response to Bacillus anthracis toxins in patients infected with cutaneous anthrax. FEMS Immunol Med Microbiol. 62(2):164-172.

Gibbons HS, Broomall S, McNew LA, Chapman C, Karavis M, McGregor P, Hong C, Akmal A, Feldman A, Lin JS, Chang WE, Higgs BW, Demirev P, Lingquist J, Liem A, Fochler E, Bishop-Lilly K, Sozhanmannan S, Rosenzweig CN, Skowronski E. 2011. Genomic signatures of strain selection and enhancement in Bacillus atrophaeus subsp. globigii, a historical biowarfare simulant. PLoS One 6(3):e17836. Chang WE, Sarver K, Higgs BW, Read TD, Nolan NME, Chapman CE, Bishop-Lilly KA, Sozhamannan S. 2011. PheMaDB: A solution for storage, retrieval and analysis of high throughput phenotypic data. BMC Bioinformatics. 12(1):109.

Larson MA, Fey PD, Bartling AM, Iwen PC, Dempsey MP, Francesconi SC, Hinrichs SH. 2011. Francisella tularensis molecular typing using differential insertion sequence amplification (DISA). J Clin Microbiol. 49(8): 2786-2797.

5. Briefly describe the biological defence work carried out at the facility, including type(s) Page 75 of 276

of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The goal of the program is the development of rapid and deployable detection assays to protect deployed troops. In a continued effort to have better prophylaxis measures, we are studying the potential use of multi-agent vaccines capable of conferring protection against multiple infectious diseases at once.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

(iii) Outdoor Studies: None

Page 76 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Research Laboratory (NRL)

2. Where is it located (provide both address and geographical location)?

4555 Overlook Ave., SW Washington, District of Columbia 20375

3. Floor area of laboratory areas by containment level:

BL2 1667 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 1667 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 48

(ii) Division of personnel:

Military 0

Civilian 48

(iii) Division of personnel by category:

Scientists 38

Engineers 5

Technicians 5

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry Biology Biophysics Chemical Engineering Chemistry Electrical Engineering Page 77 of 276

Engineering Immunology Mechanical Engineering Microbiology Molecular Biology Physics

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 17

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly National Institutes of Health (NIH)

(vii) What are the funding levels for the following program areas: Research $ 6,180,000 Development $ 2,532,000 Test and evaluation $ 0 Total $ 8,712,000

(viii) Briefly describe the publication policy of the facility: Employees are encouraged to publish. Employees must follow appropriate U.S. DoD guidelines for publishing information related to biological defense efforts and have all publications approved by the appropriate command authority. Public release of unclassified, technical information is subject to sponsor approval.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

"Spectral characterization of biological aerosol particles using two-wavelength excited laser- induced fluorescence and elastic scattering measurements", V. Sivaprakasam, H-B. Lin, A. L. Huston, and J. D. Eversole, Opt. Express, 19 (7) 6191-6208, (2011).

"Two-photon excited fluorescence from biological aerosol particles," V. Sivaprakasam, J. Luo, M. Currie, and J. D. Eversole, JQSRT 112 (2011) 1511-1517.

"Aerosol Agent Detection Using Spectroscopic Characterization" , V. Sivaprakasam, M. Page 78 of 276

Currie, J. Lou, J. Czege, and J. Eversole, Vol. 89, Suppl. No. 1, (2011) AAPP | Physical, Mathematical, and Natural Sciences.

"Single-Sided Classification: Application to Aerosol Particles Using Spectroscopic Data" Abraham Schultz, John Tucker, Tom Pierce, Roger Pierson, Jeff Willey, Marco Lanzagorta, Wendell Anderson, Paul Falkenstein and Jay Eversole, (submitted: Pattern Recognition, Dec 2011).

C. G. Hebert, A. Terray, and S. J. Hart, "Toward label-free optical fractionation of blood- optical force measurements of blood cells." Anal Chem 83(14): 5666-5672, 2011.

Qin Lu, Alex Terray, Greg E. Collins, Sean J. Hart, "Single particle analysis using fluidic, optical and electrophoretic force balance in a microfluidic system", Lab-on-a-Chip, (In press 2011).

Braden C. Giordano, Dean S. Burgi, Sean J. Hart, Alex Terray, "On-line Sample Pre- concentration in Microfluidic Devices: A Review", Analytica Chimica Acta, (Submitted 2011).

Goldman, E.R., Anderson, G.P., Zabetakis, D., Walper, S., Liu, J.L., Bernstein, R., Calm, A., Carney, J.P., O'Brien, T.W., Walker, J.L., Garber, E.A.E. 2011 Llama-derived single domain antibodies specific for Abrus Agglutinin. Toxins, 3:1405-1419.

Graef, R.R., Anderson, G.P., Doyle, K.A., Zabetakis, D., Sutton, F.N., Liu, J.L., Serrano- González, J., Goldman, E.R., Cooper, L.A. 2011 Isolation of a Highly Thermal Stable Lama Single Domain Antibody Specific for Staphylococcus aureus Enterotoxin B. BMC biotechnology, 11:86.

Swain, M.D., Anderson, G.P., Serrano-González, J., Liu, J.L., Zabatakis, D., Goldman, E.R. 2011 Immunodiagnostic Reagents using Llama Single Domain Antibody-Alkaline Phosphatase Fusion Proteins. Analytical Biochemistry, 417: 188-194.

Anderson G.P., Zabetakis D., Bernstein R.D., Cai S.W., Singh B.R., Goldman E.R. 2011 Evaluation of Anti-Hemagglutinin Hn-33 Single Domain Antibodies: Kinetics, Binding Epitopes, and Thermal Stability. The Botulinum Journal, 2:59-71.

Taitt CR, Shriver-Lake LC, Anderson GP, Ligler FS. 2011. Surface modification and biomolecule immobilization on polymer spheres for biosensing applications. Meth Mol Biol 726, 77-94.

Legler PM, Brey RN, Smallshaw JE, Vitetta ES, Millard CB (2011) Structure of RiVax: a recombinant ricin vaccine. Acta Crystallographica Section D-Biological Crystallography 67: 826-830.

Leski TA, Malanoski AP, Gregory MJ, Lin B, Stenger DA (2011) Application of a broad- Page 79 of 276

range resequencing array for detection of pathogens in desert dust samples from Kuwait and Iraq. Applied and Environmental Microbiology 77: 4285-4292.

MB. Kostova, CJ. Myers, T. Beck, BJ. Plotkin, JM. Green, HIM. Boshoff, CE. Barry III, JR. Deschamps, MI. Konaklieva. 2011. C4-Alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis Bioorganic & Medicinal Chemistry, Volume 19, Issue 22, 15 November 2011, Pages 6842-6852.

Sapsford KE, Spindel S, Jennings T, Tao G, Triulzi RC, Algar WR, Medintz IL Optimizing Two-Color Semiconductor Nanocrystal Immunoassays in Single Well Microtiter Plate Formats. Sensors (Basel). 2011;11(8):7879-7891.

Olson TY, Schwartzberg AM, Liu JL, Zhang JZ (2011) Raman and Surface-Enhanced Raman Detection of Domoic Acid and Saxitoxin. Applied Spectroscopy 65: 159-164.

Lin B, Malanoski AP, Human Coronaviruses. In Molecular Detection of Human Viral Pathogens (New York, N.Y.), Liu, D., Ed. CRC Press, Taylor & Francis Group, LLC: New York, 2011; pp 384-394.

Compton JR, Legler PM, Clingan BV, Olson MA, Millard CB Introduction of a disulfide bond leads to stabilization and crystallization of a ricin immunogen. 2011. Proteins. 2011 Apr;79(4):1048-60.

Jennings TL, Becker-Catania SG, Triulzi RC, Tao G, Scott B, Sapsford KE, Spindel S, Oh E, Jain V, Delehanty JB, Prasuhn DE, Boeneman K, Algar WR, Medintz IL. Reactive semiconductor nanocrystals for chemoselective biolabeling and multiplexed analysis. ACS Nano. 2011 Jul 26;5(7):5579-93.

Sapsford KE, Granek J, Deschamps JR, Boeneman K, Blanco-Canosa JB, Dawson PE, Susumu K, Stewart MH, Medintz IL. Monitoring botulinum neurotoxin a activity with peptide-functionalized quantum dot resonance energy transfer sensors. ACS Nano. 2011 Apr 26;5(4):2687-99.

Manka, C.K., Nikitin, S., Lunsford, R., Kunapareddy, P., Grun, J.. Wavelength Dependant Amplitude of Teflon Raman Lines, Journal of Raman Spectroscopy 42, 685 2011.

J.H. Wynne, P.A. Fulmer, D.M. McCluskey, N.M. Mackey, J.P. Buchanan, "Synthesis and Development of a Multifunctional Self-Decontaminating Polyurethane Coating", ACS Appl. Mater. Interfaces, 2011, 3(6), 2005-2011.

P.A. Fulmer, J.H. Wynne, "Development of Broad-Spectrum Antimicrobial Latex Paint Surfaces Employing Active Amphiphilic Compounds", ACS Appl. Mater. Interfaces, 2011, 3(8), 2878-2884.

N.M. Mackey, B.S. Confait, J.H. Wynne, J.P.Buchanan, "Preparation of Novel Hydrolyzing Page 80 of 276

Urethane Urethane Modified Thiol-ene Networks", Polymers, 2011, 3, 1849-1865.

P.A. Fulmer, J.H. Wynne, Cover Graphics ACS Appl. Mater. Interfaces, September 3, 2011.

Proceeding papers/published abstracts

"Covalently functionalizing graphene FETs for real-time biosensing," P. E. Sheehan, 2011 MRS Fall Meeting & Exhibit, Boston, MA, 28 Nov.-2 Dec. 2011.

"Biosensors based on chemically modified graphene," R. Stine, J. T. Robinson, P. E. Sheehan, C. R. Tamanaha, AVS 58th International Symposium & Exhibition, Nashville, TN, 30 Oct.-4 Nov. 2011.

"Real-Time, Label-Free Bio-Sensing with a Biologically Active Graphene FET," C. R. Tamanaha, R. Stine, S. P. Mulvaney, 2nd International Conference on Bio-Sensing Technology, Amsterdam, NL, 10-12, October 2011.

"Stochastic Sensing with Quantum Well Devices, BAS-BRC07-N-2-0049," C. R. Tamanaha, DTRA Chemical and Biological Defense Basic Research Technical Review, Springfield, VA, 19 July 2011.

"Using chemically modified graphene for electronics and sensing," P. E. Sheehan, W. K. Lee, A. Laracuente, S. Walton, J. Robinson, C. Tamanaha, T. L. Reinecke, Mid Atlantic Regional Meeting of the ACS 2011, College Park, MD, 21-24 May 2011.

"Functionalization of graphene for biomaterials applications using electron-beam-generated plasmas", M. Baraket, S. G. Walton, R. Stine, C. R. Tamanaha, P. E. Sheehan, J. T. Robinson, SVC 54th Annual Technical Conference, Chicago, Il, 16-21 April 2011.

"Fluidic force discrimination assays: an alternative technology for rapid and sensitive food monitoring," S. P. Mulvaney, B. J. Yakes, S. Etheridge, C. R. Tamanaha. 43rd Oakridge Conference, Baltimore, MD, 14 April 2011.

V. Sivaprakasam, M. Currie, J. Lou, J. Czege, and J. Eversole, "Aerosol Agent Detection Using Spectroscopic Characterization" Electromagnetic and Light Scattering XIII Conference, Taormina, Italy, 26-30 Sept. 2011

Walton SG, Lock EH, North SH, Taitt CR. Plasma-based approach to promote the covalent attachment of biomolecules to polymers. Soc. Vac. Coaters 2011 Tech. Conf. Proc., Chicago, Apr 2011.

Memisevic J, Shriver-Lake LC, Howell PB, Golden JP, Hashemi N, Jackson KB, Ligler FS In Automated sample processing for flow cytometry, International Workshop on Biophotonics, Parma, Italy, June 8-10, 2011; Parma, Italy, 2011; p art. no. 5954859. Page 81 of 276

Grun, J. Detecting dangerous substances from their 2D spectra, SPIE Newsroom, 10.1117/2.1201103.003600, 2011.

Patents:

Ma W, Liu JL, O'Shaughnessy T Passaged neural stem cell-derived neuronal networks as sensing elements for detection of environmental threats. US07947626, 2011.

Malanoski AP, Lin B, Schnur JM, Stenger DA Computer-implemented biological sequence identifier system and method. US7979446, 2011.

Medintz IL, Goldman ER, Anderson GP, Mauro JM Reagentless and Reusable Biosensors with Tunable Differential Binding Affinities and Methods of Making. US7927547, 2011.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The objectives are to develop and test reliable systems for the detection of biological warfare agents in order to provide early warning and contamination avoidance information.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: None

Page 82 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Naval Surface Warfare Center-Dahlgren Division Chemical, Biological, Radiological (CBR) Defense Laboratory

2. Where is it located (provide both address and geographical location)?

6149 Welsh Road Dahlgren, Virginia 22448-5162

3. Floor area of laboratory areas by containment level:

BL2 190 (sqM) BL3 26 (sqM) BL4 0 (sqM) Total laboratory floor area 216 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 171

(ii) Division of personnel:

Military 0

Civilian 171

(iii) Division of personnel by category:

Scientists 65

Engineers 52

Technicians 13

Administrative and support staff 41

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerospace Engineering Biology Chemical Engineering Chemistry Computer Engineering Page 83 of 276

Computer Science Electronic Engineering General Engineering Industrial Engineering Mathematics Mechanical Engineering Microbiology Molecular Biology Operations Research Analysis Physical Science Physics Software Engineering Toxicology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 25

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly Other Governmental Agencies Private Sector Companies Internal (Laboratory Directed Research and Development LDRD)

(vii) What are the funding levels for the following program areas: Research $ 3,222,000 Development $ 6,210,000 Test and evaluation $ 10,559,000 Total $ 19,991,000

(viii) Briefly describe the publication policy of the facility: Employees are encouraged to publish. Employees must follow appropriate U.S. DoD guidelines for publishing information related to biological defense efforts and have all publications approved. Public release of unclassified technical information is subject to sponsor approval.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.) Page 84 of 276

Andrews, A., Stelmok, B., Kinter, R., Patent: "Bernoulli Mushroom Inlet Housing for Efficient Air Sampling", Publication, May 2011.

Barnette, H., Development of the Joint Expeditionary Collective Protection (JECP) System Performance Model (SPM) Passive Filter Metamodels, Presentation, June 2011.

Barnette, H., Development of the Joint Expeditionary Collective Protection (JECP) System Performance Model (SPM) Passive Filter Metamodels, Abstract/Poster, October 2011.

Barnette, H., Joint Expeditionary Collective Protection System Performance Model(JECP SPM) Internal Model Selection Process/ Overview, Poster, April 2011.

Beck, L., Investigating Flavonoids as Radioprotectants, Poster, June 2011.

Buhr, T., Decontamination of a Hard Surface contaminated with Bacillus anthracis sterne and B. anthracis ames spores using electro-chemically generated liquid- phase chlorine dioxide (eClO2), Publication, August 2011.

Buhr, T., Hot Air Decontamination (HAD) of Bacillus spores; JBADS (Joint Biological Agent Decontamination System) Program, Presentation, June 2011.

Buhr, T., Hot Air Decontamination (HAD) of Bacillus spores; JBADS (Joint Biological Agent Decontamination System) Program, Abstract, June 2011.

Buhr, T., Hot Air Decontamination of Bacillus Spores JBADS (Joint Biological Agent Decontamination System) Program, Abstract/Poster, August 2011.

Buhr, T., Response of Bacillus thuringiensis Al Hakam Endospores to gas dynamic heating in a shock tube, Publication, June 2011.

Buhr, T., Super soap Decontamination of Biological Agents: DFOS Program, Poster, November 2011.

Buhr, T., Super Soap Decontamination of Biological Agents; DFOS (Decontamination Family of Systems) Program, Abstract/Poster, July 2011.

Clark, W., FDNY Fireboat Firefighter II CBRN System Operation and Maintenance Manual, Publication, February 2011.

Dave, G., Joint Expeditionary Collective Protection System Performance Model (JECP Page 85 of 276

SPM) Overview, Presentation, June 2011.

Dave, G., Joint Expeditionary Collective Protection System Performance Model (JECP SPM) Overview, Presentation, November 2011.

Fravel-Meyers, J., IPDS-LR Handout, Presentation, September 2011.

Fravel-Meyers, J., IPDS-LR Trifold brochure, Presentation, September 2011.

Gutting, B., and Andrews, G., Derivations of Closed Form Expressions of the Modified Brookmeyer Cumulative Distribution Function and Probability Density for Low Dose Inhalation Anthrax Incubation Period, Publication, October 2011.

Gutting, B., Evaluation of a Competing-Risks Model for Inhalation, Presentation, June 2011.

Gutting, B., Multiple Low Dose Bacillus anthracis Ames Inhalation Exposures in the Rabbit, Presentation, February 2011.

Gutting, B., Effect of Animal Sera on Bacillus Anthracis Sterne Spore, Publication, December 2011.

Hayden, R., Biological Warfare Agent Confirmatory and Pathogen Diagnostic Capabilities Via JBAIDS, Abstract/Poster, November 2011.

Hornbaker, M., Basic and Applied Science at NSWCDD Advances CBRD Capabilities to Address Current and Future Challenges, Publication, October 2011.

Hunt, J., Reactive Nanofibers for Chemical, Biological and Radiological Defense, Presentation, November 2011.

Hunt, J., Reactive Nanofibers for Chemical, Biological and Radiological Defense, abstract, June 2011.

Ketner, A., Identification of Hazard Mitigation Agents to Neutralize Dry Powder Biological Materials, Abstract/Poster, October 2011.

Ketner, A., Identification of Hazard Mitigation Agents to Neutralize Dry Powder Biological Materials, Abstract/Poster, June 2011.

Liska, B., FDNY Fireboat Three Forty Three CBRN System Operation and Maintenance Manual, Publication, July 2011.

Liska, B., Shipboard Collective Protection System Modernization for Improved Energy Page 86 of 276

Efficiency and Total ownership Cost Reduction, Presentation, May 2011.

Liska, B., Shipboard Collective Protection System Modernization for Improved Energy Efficiency and Total ownership Cost Reduction, Presentation, April 2011.

McPherson, D., Biology and Mechanics of the Bacterial Spore Coat, Publication, October 2011.

McPherson, D., Formulations to Destroy Biothreat Agents Project Overview, Presentation, November 2011.

Wells, C., Solid Oxidizer Development IPR, Presentation, April 2011.

Young, A., Hot Air Decontamination (HAD) of Bacillus Spores JBADS (Joint Biological Agent Decontamination System) Program, Presentation, August 2011.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Efforts at this defense laboratory are focused on biological detection systems, collective and individual protection systems, hazard mitigation technologies, risk assessment tools and consequence management planning.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A Priority Pathogens

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 87 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Tyndall Air Force Base -- 1

2. Where is it located (provide both address and geographical location)?

3000 Research Road Tyndall AFB, Florida 32403

3. Floor area of laboratory areas by containment level:

BL2 55 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 55 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 7

(ii) Division of personnel:

Military 1

Civilian 6

(iii) Division of personnel by category:

Scientists 5

Engineers 0

Technicians 2

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Microbiology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 5 Page 88 of 276

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Homeland Security (DHS) Other Governmental Agencies

(vii) What are the funding levels for the following program areas: Research $ 0 Development $ 0 Test and evaluation $ 0 Total $ 0 There was no 2011 funding for this program. $1.4 million was carried over from 2010 in support of the work conducted at the facility.

(viii) Briefly describe the publication policy of the facility: Unlimited release, prefer peer-reviewed journals for research results; limit to U.S. Government for test and evaluation and proprietary data

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Steven H. Hinrichs; Michael B. Lore; TeAnne L. Brown, "Biological Aerosol Test Method and Personal Protective Equipment (PPE) Decon," Annals of Occupational Hygene, May 2011.

Michael B. Lore, Brian K. Heimbuch, Teanne L. Brown, Joseph D. Wander and Steven H.

Hinrichs, "Effectiveness of Three Decontamination Treatments against Influenza Virus Applied to Filtering Facepiece Respirators," Annals of Occupational Hygene, June 2011.

Jang, "Characterization of an Decontamination by Reactive Saline Aerosols," 2011.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The facility houses and supports a bioaerosol test chamber in which aerosols containing biological simulants are used for defensive purposes to classify the size distribution of bioaerosol challenges as needed. Page 89 of 276

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 90 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Tyndall Air Force Base -- 2

2. Where is it located (provide both address and geographical location)?

139 Barnes Drive Tyndall AFB, Florida 32403

3. Floor area of laboratory areas by containment level:

BL2 53 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 53 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 21

(ii) Division of personnel:

Military 2

Civilian 19

(iii) Division of personnel by category:

Scientists 15

Engineers 1

Technicians 2

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Chemistry Environmental Engineering Microbiology

(v) Are contractor staff working in the facility? If so, provide an approximate number. Page 91 of 276

Yes Number: 13

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 395,000 Development $ 1,049,000 Test and evaluation $ 0 Total $ 1,444,000

(viii)Briefly describe the publication policy of the facility: Unlimited release, prefer peer-reviewed journals for research results; limit to U.S. Government for test and evaluation and proprietary data

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Henley, Michael; Brookins, Robert; Simpson, Katherine; Hearn, John, "Materials for Contaminated Environments," 2011.

John S. Baxley et al, "Mixed Oxidants for Chemical and Biological Decontamination," 2011.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: This facility supports the preparation and characterization of novel chemicals expected to exhibit antimicrobial properties. It also supports research into degradation products formed by exposure of samples of reactive materials to simulant threat agents.

(ii) Agents Microorganisms and/or Toxins: None

(iii) Outdoor Studies: None

Page 92 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Edgewood Chemical and Biological Center

2. Where is it located (provide both address and geographical location)?

5183 Blackhawk Road Aberdeen Proving Ground, Maryland 21010-5424

3. Floor area of laboratory areas by containment level:

BL2 532 (sqM) BL3 177 (sqM) BL4 0 (sqM) Total laboratory floor area 709 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 291

(ii) Division of personnel:

Military 0

Civilian 291

(iii) Division of personnel by category:

Scientists 168

Engineers 39

Technicians 28

Administrative and support staff 56

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology Aerospace Engineering Biochemistry Biology Biomedical Engineering Biotechnology Page 93 of 276

Chemical Engineering Chemistry Computer Engineering Electronic Engineering General Engineering Immunology Mathematics Mechanical Engineering Microbiology Molecular Biology Operations Research Analysis Physical Science Physics Physiology Statistics Toxicology Toxinology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 127

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 1,270,000 Development $ 21,403,000 Test and evaluation $ 0 Total $ 22,673,000

(viii) Briefly describe the publication policy of the facility: Publications are prepared in accordance with Army regulations. Scientists are encouraged to publish their results in peer-reviewed scientific literature as well as present their work at national and international professional meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work Page 94 of 276

during the previous 12 months. (To include authors, titles, and full references.)

Emanuel P., Jones F., Smith M., Huff W., Jaffe R., and Roos J. The key to enabling biosurveillance is cooperative technology development. Biosecur. Bioterror. 2011, Dec; 9(4):386-393. Epub 7 Nov 2011.

Hubbard K., Pellar G., and Emanuel P. Suitability of Commercial Transport Media for Biological Pathogens under Nonideal Conditions. Int. J. Microbiol. 2011; 463096. Epub 30 Oct 2011.

Jabbour, Rabih. Mass spectrometry for microbial proteomics. Ed: Haroun N. Shah and Saheer E. Gharbia. Analytical and Bioanalytical Chemistry 2011, 400(7), 1815-1816.

Jabbour, Rabih E.; Deshpande, Samir V.; Stanford, Michael F.; Wick, Charles H.; Zulich, Alan W.; Snyder, A. Peter. A Protein Processing Filter Method for Bacterial Identification by Mass Spectrometry-Based Proteomics. Journal of Proteome Research 2011, 10(2), 907- 912.

Sagripanti, Jose-Luis; Carrera, Monica; Robertson, Jeannie; Levy, Avram; Inglis, Timothy J. J. Size distribution and buoyant density of Burkholderia pseudomallei. Archives of Microbiology 2011, 193(1), 69-75. Sagripanti J.L., Hülseweh B., Grote G., Voss L., Böhling K., and Marschall H.J. Microbial inactivation for safe and rapid diagnostics of infectious samples. Appl. Environ. Microbiol. 2011, Oct; 77(20):7289-95. Epub 19 Aug 2011.

Sagripanti J.L., Marschall H.J., Voss L., and Hülseweh B. Photochemical inactivation of alpha- and poxviruses. Photochem. Photobiol. 2011, Nov-Dec; 87(6):1369-78. Epub 3 Oct 2011.

Sagripanti J.L., Grote G., Niederwöhrmeier B., Hülseweh B., and Marschall H.J. Photochemical Inactivation of Pseudomonas aeruginosa. Photochem. Photobiol. 2011, Nov 4. Epub ahead of print.

Wade, Mary Margaret; Biggs, Tracey D.; Insalaco, Joseph M.; Neuendorff, Lisa K.; Bevilacqua, Vicky L.H.; Schenning, Amanda M.; Reilly, Lisa M.; Shah, Saumil S.; Conley, Edward K.; Emanuel, Peter A.; and Zulich Alan W. Evaluation of handheld assays for the detection of ricin and Staphylococcal enterotoxin B in disinfected waters. Int. J. Microbiol. 2011, 132627, 5pp. Epub 14 July 2011.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives:

Page 95 of 276

Development of non-medical defensive material against biological agents to include: research, development, and engineering for methods of rapid detection, identification, decontamination, and physical protection from biological threat agents.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B Priority Pathogens

(iii) Outdoor Studies: Yes-using simulants

Page 96 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Medical Research Institute of Chemical Defense (USAMRICD)

2. Where is it located (provide both address and geographical location)?

3100 Ricketts Point Road Aberdeen Proving Ground, Maryland 21010-5400

3. Floor area of laboratory areas by containment level:

BL2 300 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 300 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 11

(ii) Division of personnel:

Military 1

Civilian 10

(iii) Division of personnel by category:

Scientists 5

Engineers 0

Technicians 6

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry Biology Molecular Biology Pharmacology Physiology Page 97 of 276

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 1,399,000 Development $ 0 Test and evaluation $ 0 Total $ 1,399,000

(viii) Briefly describe the publication policy of the facility:

Publications are prepared and published in accordance with Army regulations.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Lebeda, FL, Dembek, ZF, Adler, M. Kinetic and reaction pathway analysis in the application of botulinum toxin A for wound healing. J. Toxicol. 2012:1-9. Epub 2011 Nov 24.

Wilder-Kofie, TD, Luquez, C., Adler, M., Kykes, JK, Coleman, JD, Maslanka, SE. An alternative in vivo method to refine the mouse bioassay for botulinum toxin detection. Comp. Med. 2011, 61:235-242.

P McNutt, J Celver, T Hamilton, M Mesngon. Embryonic stem cell-derived neurons are a novel, highly sensitive tissue culture platform for botulinum research. Biochemical and Biophysical Research Communications. 2011, 405, 85-90.

M Mesngon, P McNutt. Alpha-latrotoxin rescues SNAP-25 from BoNT/A-mediated proteolysis in embryonic stem cell-derived neurons. Toxins 2011, 3, 489-503.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols. Page 98 of 276

(i) Objectives: The Institute's mission involves research on medical defenses against neurotoxins.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A Priority Pathogens

(iii) Outdoor Studies: None

Page 99 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)

2. Where is it located (provide both address and geographical location)?

1425 Porter Street Fort Detrick

Frederick, Maryland 21702-5011

3. Floor area of laboratory areas by containment level:

BL2 26026 (sqM) BL3 3139 (sqM) BL4 1186 (sqM) Total laboratory floor area 30351 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 837

(ii) Division of personnel:

Military 212

Civilian 625

(iii) Division of personnel by category:

Scientists 282

Engineers 5

Technicians 302

Administrative and support staff 248

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology Biochemistry Biology Chemistry Clinical Immunology Page 100 of 276

Entomology Genetics Immunology Infectious Disease Internal Medicine Microbiology Molecular Biology Preventive Medicine Toxicology Veterinary Medicine Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 259

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 4,266,000 Development $ 47,533,000 Test and evaluation $ 7,785,000 Total $ 59,584,000

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Akhvlediani T, Ellis MW, Rivard R, Zenaishvili O, Battafarano DJ, Hepburn MJ. A review of the english and Russian language literature on the osteoarticular manifestations of brucellosis infection. Current Rheumatology Reviews 2011, 7(3): 263-271. Badger CV, Richardson JD, DaSilva RL, Richards MJ, Josleyn MD, Dupuy LC, Hooper Page 101 of 276

JW, Schmaljohn CS. Development and application of a flow cytometric potency assay for DNA vaccines. Vaccine 2011 Sept 9, 29(39): 6728-6735.

Bahta M, Lountos GT, Dyas B, Kim SE, Ulrich RG, Waugh DS, Burke TR. Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase. Journal of Medicinal Chemistry 2011 Apr 28; 54(8): 2933-43.

Basu A; Li B; Mills DM; Panchal RG; Cardinale SC; Butler MM; Peet NP; Majgier- Baranowska H; Williams JD; Patel I; Moir DT; Bavari S; Ray R; Farzan MR; Rong LJ; Bowlin TL. Identification of a small-molecule entry inhibitor for filoviruses. Journal of Virology 2011 Apr, 85(7): 3106-3119.

Bondugula R, Wallqvist A, Lee MS. Can computationally designed protein sequences improve secondary structure prediction? Protein Engineering Design & Selection 2011 May; 24(5): 455-61.

Bozue J, Mou S, Moody KL, Cote CK, Trevino S, Fritz D, Worsham P. The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis. Microbial Pathogenesis 2011 June; 50(6): 314-21.

Bradfute SB, Bavari S. Correlates of Immunity to Filovirus Infection. Viruses-Basel 2011 July, 3(7): 982-1000.

Bradfute SB, Dye JM, Bavari S. Filovirus vaccines. Human Vaccines 2011 June; 7 (6): 701- 711.

Bradfute SB, Stuthman KS, Shurtleff AC, Bavari S. A STAT-1 knockout mouse model for Machupo virus pathogenesis. Virology Journal 2011 June 14; 8: 300.

Brett PJ; Burtnick MN; Heiss C; Azadi P; DeShazer D; Woods DE; Gherardini FC. Burkholderia thailandensis oacA mutants facilitate the expression of Burkholderia mallei- like O polysaccharides. Infection and Immunity 2011 Feb, 79(2): 961-969.

Burke RL, Vest KG, Eick AA, Sanchez JL, Johns MC, Pavlin JA, Jarman RG, Mothershead JL, Quintana M, Palys T, Cooper MJ, Guan J, Schnabel D, Waitumbi J, Wilma A, Daniels C, Brown ML, Tobias S, Kasper MR, Williams M, Tjaden JA, Oyofo B, Styles T, Blair PJ, Hawksworth A, Montgomery JM, Razuri H, Laguna-Torres A, Schoepp RJ, Norwood DA, MacIntosh VH, Gibbons T, Gray GC, Blazes DL, Russel, KL. Department of Defense influenza and other respiratory disease surveillance during the 2009 pandemic. BMC Public Health 2011 Mar 4; 11 (Suppl. 2): S6.

Burtnick MN; Brett PJ; Harding SV; Ngugi SA; Ribot WJ; Chantratita N; Scorpio A; Milne TS; Dean RE; Fritz DL; Peacock SJ; Prior JL; Atkins TP; Deshazer D. The cluster 1 type VI Page 102 of 276

secretion system is a major virulence determinant in Burkholderia pseudomallei. Infection and Immunity 2011 Apr, 79(4): 1512-25.

Cardellina JH, Vieira RC, Eccard V, Skerry J, Montgomery V, Campbell Y, Roxas-Duncan V, Leister W, Leclair CA, Maloney DJ, Padula D, Pescitelli G, Khavrutskii I, Hu X, Wallqvist A, Smith LA. Separation of betti reaction produt enantiomers: Absolute configuration and inhibition of botulinum neurotoxin A. ACS Medicinal Chemistry Letters 2011 May 12; 2(5): 396-401.

Cardinale SC, Butler MM, Ruthel G, Nuss J, Wanner LM, Li B, Pai RP, Peet NP, Bavari S, Bowlin TL. Novel benzimidazole inhibitors of botulinum neurotoxin/A display enzyme and cell-based potency. Botulinum Journal 2011 2(1): 16-29.

Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 2011 Sept 15, 477(7364): 340-43.

Carman RJ, Stevens AL, Lyerly MW, Hiltonsmith MF, Stiles BG, Wilkins TD. Clostridium difficile binary toxin (CDT) and diarrhea. Anaerobe 2011 Aug, 17(4): 161-165.

Cashman KA; Smith MA; Twenhafel NA; Larson RA; Jones KF; Allen RD; Dai D; Chinsangaram J; Bolken TC; Hruby DE; Amberg SM; Hensley LE; Guttieri MC. Evaluation of Lassa antiviral compound ST-193 in a guinea pig model. Antiviral Research 2011 Apr, 90(1): 70-9.

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Shurtleff AC, Warren TK, Bavari S. Nonhuman primates as models for the discovery and development of ebolavirus therapeutics. Expert Opinion on Drug Discovery 2011 Mar; 6 (3): 233-250.

Simpson-Holley M; Kedersha N; Dower K; Rubins KH; Anderson P; Hensley LE; Connor JH. Formation of antiviral cytoplasmic granules during Orthopoxvirus infection. Journal of Virology 2011 Feb, 85(4): 1581-1593.

Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8(+) cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nature Medicine 2011 Sept, 17(9): 1128-1131.

Swietnicki W, Carmany D, Retford M, Guelta M, Dorsey R, Bozue J, Lee MS, Olson MA. Identification of Small-Molecule Inhibitors of Yersinia pestis Type III Secretion System YscN ATPase. PLoS One 2011 May 18; 6(5): e19716.

Tubaro A, Del Favero G, Beltramo D, Ardizzone M, Forino M, De Bortoli M, Pelin, M, Poli M, Bignami G, Ciminiello P, Sosa S. Acute oral toxicity in mice of a new palytoxin analog: 42-Hydroxy-palytoxin. Toxicon 2011 Apr; 57(5): 755-63.

Turell M, Davé K, Mayda M, Parker Z, Coleman R, Davé S, Strickman D. Wicking assay for the rapid detection of rift valley fever viral antigens in mosquitoes (diptera: Culicidae). Journal of Medical Entomology 2011 May; 48(3): 628-33. Page 113 of 276

Vernati G; Edwards WH; Rocke TE; Little SF; Andrews GP. Antigenic profiling of Yersinia pestis infection in the Wyoming coyote (Canis Latrans). Journal of Wildlife Diseases 2011 Jan, 47(1): 21-29.

Wahl-Jensen V, Cann JA, Rubins KH, Huggins JW, Fisher RW, Johnson AJ, de Kok- Mercado F, Larsen T, Raymond JL, Hensley LE, Jahrling PB. Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus. PLoS One 2011 Oct; 6 (10): e24832.

Wanja E, Parker Z, Rowland T, Turell MJ, Clark JW, Davé K, Davé S, Sang R. Field evaluation of a wicking assay for the rapid detection of rift valley fever viral antigens in mosquitoes1. Journal of the American Mosquito Control Association 2011 Dec; 27 (4): 370- 375.

Weinstein SA, Stiles BG. A review of the epidemiology, diagnosis and evidence-based management of Mycoplasma genitalium. Sexual Health 2011 June; 8(2): 143-158.

Welkos S, Cote CK, Hahn U, Shastak O, Jedermann J, Bozue J, Jung G, Ruchala P, Pratikhya P, Tang T, Lehrer RI, Beyer W. Humanized theta-Defensins (Retrocyclins) Enhance Macrophage Performance and Protect Mice from Experimental Anthrax Infections. Antimicrobial Agents and Chemotherapy 2011 Sept 11, 55(9): 4238-4250.

Williamson ED, Packer PJ, Waters EL, Simpson AJ, Dyer D, Hartings J, Twenhafel N, Pitt MLM. Recombinant (F1+V) vaccine protects cynomolgus macaques against pneumonic plague. Vaccine 2011 June 24, 29(29-30): 4771-4777.

Wink DA, Hines HB, Cheng RYS, Switzer CH, Flores-Santana W, Vitek MP, Ridnour LA, Colton CA. Nitric oxide and redox mechanisms in the immune response. Journal of Leukocyte Biology 2011; 89(6): 873-891.

Wolfe LL, Shenk TM, Powell B, Rocke TE. Assessment of a Recombinant F1-V Fusion Protein Vaccine Intended to Protect Canada Lynx (Lyns Canadensis) from Plague. Journal of Wildlife Diseases 2011 Oct; 47(4): 888-892.

Wu SJ, Eiben CB, Carra JH, Huang I, Zong D, Liu PX, Wu CT, Nivala J, Dunbar J, Huber T, Senft J, Schokman R, Smith MD, Mills JH, Friedlander AM, Baker D, Siegel JB. Improvement of a Potential Anthrax Therapeutic by Computational Protein Design. Journal of Biological Chemistry 2011 Sept 16, 286(37): 32586-32592.

Yakes BJ, DeGrasse SL, Poli M, Deeds JR. Antibody characterization and immunoassays for palytoxin using an SPR biosensor. Analytical and Bioanalytical Chemistry 2011 July; 400(9): 2865-2869.

Yen JY, Garamszegi S, Geisbert JB, Rubins KH, Geisbert TW, Honko A, Xia Y, Connor JH, Hensley LE. Therapeutics of Ebola Hemorrhagic Fever: Whole-Genome Transcriptional Page 114 of 276

Analysis of Successful Disease Mitigation. Journal of Infectious Diseases 2011 Nov; 204(Suppl 3): S1043-S1052.

Zeitlin L, Pettitt J, Scully C, Bohorova N, Kim D, Pauly M, Hiatt A, Ngo L, Steinkellner H, Whaley KJ, Olinger GG. Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proceedings of the National Academy of Science USA 2011 Dec 20; 108(51): 20690-4.

Zumbrun EE, Friedman HM. An attenuated HSV-1 live virus vaccine candidate that is replication competent but defective in epithelial cell-to-cell and neuronal spread. Birkhauser Advances in Infectious Diseases 2011, 3: 223-236.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: To develop medical countermeasures, to include candidate vaccines, diagnostic tests and drug or immunological therapies for biological agents. Perform exploratory studies and advanced development of protective and therapeutic countermeasures and agent identification technologies.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 115 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Walter Reed Army Institute of Research (WRAIR)

2. Where is it located (provide both address and geographical location)?

503 Robert Grant Avenue Silver Spring, Maryland 20910

3. Floor area of laboratory areas by containment level:

BL2 294 (sqM) BL3 165 (sqM) BL4 0 (sqM) Total laboratory floor area 459 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 19

(ii) Division of personnel:

Military 3

Civilian 16

(iii) Division of personnel by category:

Scientists 7

Engineers 0

Technicians 12

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerobiology Immunology Microbiology Molecular Biology

(v) Are contractor staff working in the facility? If so, provide an approximate Page 116 of 276

number.

Yes Number: 10

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - wholly

(vii) What are the funding levels for the following program areas: Research $ 2,080,000 Development $ 0 Test and evaluation $ 0 Total $ 2,080,000

(viii) Briefly describe the publication policy of the facility: Publications are prepared in accordance with Army regulations and receive in-house peer- review before the article is published. Scientists are encouraged to publish and present their results in the open scientific literature and at scientific meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Ake J, Scott P, Wortmann G, Huang XZ, Barber M, Wang Z, Nikolich M, Van Echo D, Weintrob A, Lesho E. 2011. Gram-negative multidrug-resistant organism colonization in a US military healthcare facility in Iraq. Infect Control Hosp Epidemiol. 32(6):545-52.

Filippov AA, Sergueev KV, He Y, Huang XZ, Gnade BT, Mueller AJ, Fernandez-Prada CM, Nikolich MP. Bacteriophage-resistant mutants in Yersinia pestis: identification of phage receptors and attenuation for mice. PLoS One. 2011, 6(9):e25486. Epub 2011 Sep 28.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The Walter Reed Army Institute of Research conducts research on bacterial threat agents, including the study of therapeutics against these agents. Biological defense work at WRAIR was moved to Fort Detrick to comply with U.S. Base Realignment and Closure law. WRAIR had a biological defense program from January 2011 to August 2011.

Page 117 of 276

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

(iii) Outdoor Studies: None

Page 118 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Brookhaven National Laboratory

2. Where is it located (provide both address and geographical location)?

Brookhaven National Laboratory Biology Department

Upton, New York 11973-5000

3. Floor area of laboratory areas by containment level:

BL2 185 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 185 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 18

(ii) Division of personnel:

Military 0

Civilian 18

(iii) Division of personnel by category:

Scientists 14

Engineers 0

Technicians 4

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry Biomedical Science Cell Biology Epigenetics Genetics Page 119 of 276

Genomics Molecular Biology Neuroscience Protein Chemistry Protein Crystallography Protein Engineering Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 14

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) Internal (Laboratory Directed Research and Development LDRD) Other Governmental Agencies

(vii) What are the funding levels for the following program areas: Research $ 6,343,000 Development $ 0 Test and evaluation $ 0 Total $ 6,343,000

(viii) Briefly describe the publication policy of the facility: It is the policy of Brookhavan National Laboratory that the results of research be published unless publication is expressly restricted by written agreement and that such publication is an essential part of the work of the Laboratory. The preparation of reviews articles monographs etc requested by sponsoring organizations and related to sponsored work is considered part of the regular duties of the scientific and technical staff members. Scientists are required to publish their results in the peer reviewed scientific literature as well as present their work at national and international meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Botcheva, Krassimira, Sean R. McCorkle, W.R. McCombie, John J. Dunn and Carl W. Page 120 of 276

Anderson. Distinct p53 genomic binding patterns in normal and cancer-derived human cells. Cell Cycle 10: 24 pp4237-4249 (2011).

Scotto-Lavino, E., Bai, M., Zhang, Y.-B., and Freimuth, P. Export is the default pathway for soluble unfolded polypeptides that accumulate during expression in Escherichia coli. Protein Expression and Purification 79(1): 137-141 (September, 2011).

Lebel E.A., Rusek A., Sivertz M.B., Yip K., Thompson K.H., and Tafrov S.T. Analyses of the secondary particle radiation and the DNA damage it causes to human keratinocytes. J. Radiat. Res. (Tokyo), 52(6):685-693 (2011).

Zhang L.R., Sun W.M., Wang J.J., Zhang M., Yang S.M., Tian Y.P., Vidyasagar S., Pena L.A., Zhang K.Z., et al., Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation., Int J Radiat Oncol Biol Phys., 77(1);261-268 (2010).

Thomas, M. F., Li, L. L., Handley-Pendleton, J. M., van der Lelie, D., Dunn, J. J., and Wishart, J. F. Enzyme activity in dialkyl phosphate ionic liquids. Bioresource Technology 102(24): 11200-11203 (December, 2011).

Bagaria, A., Kumaran, D., Burley, S. K., and Swaminathan, S. Structural basis for a ribofuranosyl binding protein: Insights into the furanose specific transport. PROTEINS: Structure, Function, and Bioinformatics 79(4): 1352-1357 (April, 2011).

Hale, M., Oyler, G., Swaminathan, S., and Ahmed, S. A. Basic tetrapeptides as potent intracellular inhibitors of type A Botulinum neurotoxin protease activity. Journal of Biological Chemistry 286(3): 1802-1811 (January, 2011).

Kamat, S. S., Holmes-Hampton, G. P., Bagaria, A., Kumaran, D., Tichy, S. E., Gheyi, T., Zheng, X., Bain, K., Groshong, C., Emtage, S., Sauder, J. M., Burley, S. K., Swaminathan, S., Lindahl, P. A., and Raushel, F. M. The catalase activity of diiron adenine deaminase. Protein Science 20(12): 2080-2094 (December, 2011).

Swaminathan, S. Molecular structures and functional relationships in clostridial neurotoxins. FEBS Journal 278(23): 4467-4485 (December, 2011).

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The majority of the agents are not used for biodefense related work. The overall objective of the project that is biodefense related (DOD supported) is to develop countermeasures for

biowarfare agents. The specific aim of the project is to determine the three-dimensional structures of the agents. The purified agents are crystallized using standard crystallization Page 121 of 276

techniques and brought to the National Synchrotron Light Sources (also at Brookhaven National Laboratory) for x-ray diffraction studies. These results can lead to vaccine development, treatment, and/or diagnosis. BNL is registered with the CDC Select Agent Program for this work.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A Priority Pathogens

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 122 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Idaho National Laboratory

2. Where is it located (provide both address and geographical location)?

Idaho National Laboratory 2525 Fremont Ave.

Idaho Falls, Idaho 83415-2203

3. Floor area of laboratory areas by containment level:

BL2 90 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 90 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 6

(ii) Division of personnel:

Military 0

Civilian 6

(iii) Division of personnel by category:

Scientists 6

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Genomics Microbiology Molecular Biology Wildlife Health-Decontamination Efficacy Study Page 123 of 276

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Homeland Security (DHS) U.S. Environmental Protection Agency (EPA)

(vii) What are the funding levels for the following program areas: Research $ 0 Development $ 0 Test and evaluation $ 280,000 Total $ 280,000

(viii)Briefly describe the publication policy of the facility: Publication is encouraged but must meet customer requirements and export control restrictions.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

None published during that period.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Viability testing subsequent to decontamination using Bacillus atrophaeus as a simulant for B. anthracis. No funded work with Brucella in 2011, but viable culture collection is maintained.

(ii) Agents Microorganisms and/or Toxins: • Overlap Select Agents Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Page 124 of 276

(iii) Outdoor Studies: None

Page 125 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lawrence Berkeley National Laboratory (LBNL)

2. Where is it located (provide both address and geographical location)?

Lawrence Berkeley National Lab 1 Cyclotron Road

Berkeley, California 94720

3. Floor area of laboratory areas by containment level:

BL2 130 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 130 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 6

(ii) Division of personnel:

Military 0

Civilian 6

(iii) Division of personnel by category:

Scientists 3

Engineers 0

Technicians 3

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology Bioinformatics Biology Computational Biology Ecology Page 126 of 276

Environmental Science Genomics Microbial Forensics Microbiology Molecular Biology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas: Research $ 200,000 Development $ 0 Test and evaluation $ 0 Total $ 200,000

(viii) Briefly describe the publication policy of the facility: The mission of Lawrence Berkeley National Laboratory is to generate and disseminate knowledge in the public interest. Essential to this mission are two fundamental principles: open scholarly exchange and academic freedom. Normally, these principles are mutually supportive. On those rare occasions when they conflict, they must be balanced, taking into account LBNL's mission and the public interest. LBNL has also has had a longstanding tradition of conducting research aimed at enhancing human life and the human condition.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

None

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: No biological defense work currently. We are writing manuscripts from previous biological Page 127 of 276

defense work on strain typing in Francisella. We currently have no live isolates or DNA from any Select Agent.

(ii) Agents Microorganisms and/or Toxins: None

(iii) Outdoor Studies: None

Page 128 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Lawrence Livermore National Laboratory (LLNL)

2. Where is it located (provide both address and geographical location)?

Lawrence Livermore National Laboratory 7000 East Avenue

Livermore, California 94550

3. Floor area of laboratory areas by containment level:

BL2 1414 (sqM) BL3 60 (sqM) BL4 0 (sqM) Total laboratory floor area 1474 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 124

(ii) Division of personnel:

Military 0

Civilian 124

(iii) Division of personnel by category:

Scientists 78

Engineers 3

Technicians 17

Administrative and support staff 26

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerosol Science Analytical Biochemistry Analytical Mass Spectrometry Bacteriology Biochemistry Page 129 of 276

Bioengineering Bioinformatics Biology Biomedical Engineering Biomedical Science Biophysics Biotechnology Chemical Engineering Chemistry Computer Science Environmental Science Epidemiology Immunology Infectious Disease Mass Spectrometry Mass Spectrometry Biochemistry Microbial Forensics Microbiology Microfluidics Molecular Biology Molecular Computational Biology Nanotechnology Pharmacology Plant Biotechnology Proteomics Toxicology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) U.S. Environmental Protection Agency (EPA) Internal (Laboratory Directed Research and Development LDRD) Other Governmental Agencies Page 130 of 276

(vii) What are the funding levels for the following program areas: Research $ 23,514,000 Development $ 0 Test and evaluation $ 3,495,000 Total $ 27,009,000

(viii) Briefly describe the publication policy of the facility: Lawrence Livermore National Laboratory's (LLNL) publication policy is contained in the "LLNL Information Management Policy" (January 2008). Prior to publication, document content including scientific, technical and programmatic information is reviewed and released by the author's directorate, the Office of Classification and Export Control, and/or the Industrial Partnerships Office, as appropriate. Subject matter experts may also be required to review documents based on the content. Every year, authors at LLNL create thousands of documents. These documents are widely varied in scientific, technical, programmatic, and administrative content and scope. Some documents are written for the scientific community outside the Laboratory and some are written for the general public. Some documents are written for a more limited audience. Reviews are conducted prior to publication to determine availability of information, or restrictions thereto. These reviews include, but are not limited to, the following: 1) classification/declassification, 2) copyrighted materials or other intellectual property, 3) export controls or distribution restrictions, and 4) sensitive content that limits access. The LLNL Information Management Policy ensures that unclassified and classified scientific and technical information resulting from LLNL research is identified, processed, disseminated, and preserved in accordance with our contract and DOE requirements.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Characterization of a Novel Endolytic Protein, AMPD BCZK2532 as a Bacillus Anthracis Antimicrobial Protein, Feliza A. Bourguet, LLNL; Brian E. Souza, LLNL; Matthew A. Coleman, LLNL; Paul J. Jackson, LLNL Mechanisms of Antibiotic Resistance in Burkholderia thailandensis, M. J. Pavlovich, LLNL; L. M. Vergez, LLNL; P. J. Jackson, LLNL.

Characterization of a Novel Bacterial Protein Encoded by the Bacillus Anthracis Genome, Paul J. Jackson, LLNL.

Antibiotic Resistance Mutation Discovery Using Tiling Arrays and High-Throughput Sequencing, K. S. McLoughlin, LLNL; S. N. Gardner, LLNL; C. J. Jaing, LLNL; T. R. Slezak, LLNL.

Applications of Microarrays: Identifying Viral Pathogens, S. S. D'Souza, Johns Hopkins Page 131 of 276

University; J. B. Thissen, LLNL; S. L. Mabery, LLNL; K. S. McLoughlin, LLNL; S. N. Gardner, LLNL; T. Slezak, LLNL; C. J. Jaing, LLNL.

Antibiotic Resistance Mutation Discovery Using Tiling Microarrays and High-Throughput Sequencing, K. McLoughlin, LLNL.

Identification of SNPs Responsible for Antibiotic Resistance in Biothreat Agents by DNA Microarrays and Illumina Sequencing, J. Thissen, LLNL; C. Jaing, LLNL; L. Vergez, LLNL; F. Bourguet, LLNL; K. Mcloughlin, LLNL; S. Mabery, LLNL; P. J. Jackson, LLNL.

Validation of Biological Agent Sample Matching Using Elemental Composition Data Applied to trace and bulk samples, P. K. Weber, LLNL; S. P. Velsko, LLNL; M. L. Davisson, LLNL.

Genetic Inference on Disease Transmission Networks, S. P. Velsko, LLNL Non-genetic sample characterization technologies, S. P. Velsko, LLNL BioForensics Overview, S. P. Velsko, LLNL.

NanoSIMS analysis of Bacillus spores for forensics, P. K. Weber, LLNL; M. L. Davisson, LLNL; S. P. Velsko, LLNL.

Non-biological measurements on biological agents, S. P. Velsko, LLNL.

Inferential validation and evidence interpretation, S. P. Velsko, LLNL.

Spore Dating Using the Carbon-14 Bomb Pulse, B. A. Buchholz, LLNL; J. A. Cappuccio, LLNL; M. J. Sarachine, LLNL.

Development of Luminex-Based Applications for Biodefense, J. M. Dzenitis, LLNL.

Challenges to Detecting Pathogens in Food and Molecular Assays to Address Some of Them, P. Naraghi-Arani, LLNL.

Point-of-care diagnostic for FMDV, P. Naraghi-Arani, LLNL; J. Bearinger, LLNL; L. Dugan, LLNL; B. Baker, LLNL; S. Hall, LLNL.

Testing of TaqMan Signatures for Use in the Deterction of Bacillus anthracis, P. Bales, LLNL; C. Carrillo, LLNL; P. Naraghi-Arani, LLNL.

Quantitative Molecular Assays [TTA-1], P. Naraghi-Arani, LLNL.

Multiplexed Diagnostic Assays for Detection of High Consequence Foreign and Emerging Animal Disease, A. Carrillo, LLNL; K. Pitz, LLNL; J. Thissen, LLNL; J. Olivas, LLNL; B. Harrel, LLNL; M. El Sheikh, LLNL; M. Rasmussen, LLNL; R. Lenhoff, LLNL; P. Naraghi- Page 132 of 276

Arani, LLNL.

Navigating Dante's Inferno: Creation of Signatures for the Rapid Detection of Hemorrhagic Fever Agents, K. Pitz, LLNL; C. Carrillo, LLNL; J. Thissen, LLNL; J. Olivas, LLNL; B. Harrel, LLNL; M. El Sheikh, LLNL; R. Lenhoff, LLNL; P. Naraghi-Arani, LLNL.

Identification of Novel MicroRNA Biomarkers of Viral Infection, P. Naraghi-Arani, LLNL; S. Gardner, LLNL; C. Jaing, LLNL; S. Bavari, LLNL.

Fundamental investigation of carbon-nanotube nanofluidic phenomena for single molecule detection, F. Fornasiero, LLNL; S. Letant, LLNL; Z. Siwy, UC Irvine; N. Aluru, UIUC.

Enhancing breathability and protection of membrane materials using carbon nanotubes, Y. M. Wang, LLNL.

Nanofluidics in Carbon Nanotube Pores, F. Fornasiero, LLNL.

Surface Phenomena and Parameters of Crystal Growth: Simple Basics, A. A. Chernov, LLNL Bioinformatics & Biodefense, T. Slezak, LLNL.

Design of Genomic Signatures of Pathogen Identification & Characterization, T. Slezak, LLNL; S. Gardner, LLNL; J. Allen, LLNL; E. Vitalis, LLNL; C. Jaing, LLNL.

Application of genotyping, microarray and sequencing technologies to detect biothreat agents from complex environmental samples, C. Jaing, LLNL; J. Thissen, LLNL; J. Wollard, LLNL; A. Hinckley, LLNL; P. Jackson, LLNL.

Microarrays Rapidly Detect Bacterial and Viral Pathogens, C. Jaing, LLNL; S. Gardner, LLNL; K. McLoughlin, LLNL; J. Thissen, LLNL; T. Slezak, LLNL.

Determining Absorption, Distribution, and Elimination of Radiolabeled Nanoparticles with Accelerator Mass Spectrometry, M. Malfatti, LLNL; E. Kuhn, LLNL; W. Wang, Oak Ridge National Laboratory; S. Retterer, Oak Ridge National Laboratory; K. Turteltaub, LLNL.

Combining Knowledge of Viral Evolution and Epidemiology to Identify the Source of a Viral Outbreak, J. Allen, LLNL; S. Velsko, LLNL; J. Osburne, LLNL; K. Kim, LLNL; M. Pitluck, LLNL.

Application of a Lawrence Livermore Microbial Detection Array (LLMDA) in Biodefense and Public Health, C. Jaing, LLNL; J. Thissen, LLNL; S. Gardner, LLNL; K. McLoughlin, LLNL; T. Slezak, LLNL.

Challenges in genomic based approaches for genetic engineering detection, J. Allen, LLNL; T. Slezak, LLNL. Page 133 of 276

Bioinformatics tools for microbial genotyping that scale to handle hundreds of genomes, S. Gardner, LLNL; C. Jaing, LLNL; K. McLoughlin, LLNL; T. Slezak, LLNL.

System Studies to define and fill genomic sequence knowledge gaps for the Transformational Medical Technologies (TMT) program, T. Slezak, LLNL; M. Borucki, LLNL; R. Lenhoff, LLNL; E. Vitalis, LLNL.

Bioinformatics: The backbone of LLNL's Biodefense program, T. Slezak, LLNL BioThreat Response Vehicle, T. Bunt, LLNL.

LLNL's Role in the Department of Homeland Security BioWatch Program, T. Bunt, LLNL National Capital Region (NCR) BioWatch Laboratory, T. Bunt, LLNL; S. Kane, LLNL.

Detection of Francisella tularensis Volatile Emissions During Infection of Human Monocytes by Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry, J. S. Reich, LLNL; A. S. Mostaghim, LLNL; D. J. Kennedy, LLNL; A. Lin, LLNL; R. N. Udey, LLNL; A. M. Williams, LLNL; G. R. Farquar, LLNL; A. Rasley, LLNL ; M. Frank, LLNL.

Breath Analysis for National Security Applications: Emerging Biometrics and Forensics, G. Farquar, LLNL; M. Frank, LLNL.

Bio-threat Simulants Produced with Food Additives and DNA for the Testing of Biodetector Networks, R. N. Udey, LLNL; C. A. Hara, LLNL; E. D. Wheeler, LLNL; C. B. Thomas, LLNL; A. D. Jones, Michigan State University; G. R. Farquar, LLNL.

Detection of Francisella tularensis Volatile Emissions by Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry, R. N. Udey, LLNL; A. M. Williams, LLNL; G. R. Farquar, LLNL; A. Rasley, LLNL; M. Frank, LLNL.

Bio-threat Simulants produced with FDA food additives containing DNA for the testing of bio-detector networks, G. Farquar, LLNL.

Bioinformatics for Post-Sequencing BWA Threat Characterization, Including Genetic Engineering, M. W. Torres, LLNL; J. K. Sirp, LLNL; C. L. Torres, LLNL; R. M. Moore, LLNL; L. E. Banks, LLNL; M. C. Wagner, LLNL; T. R. Slezak, LLNL LLNL.

Microarrays for Pathogen Detection, Characterization, and Forensic Analysis, C. Jaing, LLNL; T. Slezak, LLNL; H. Franz, LLNL.

MvirDB-a microbial database of protein toxins, virulence factors and antibiotic resistance genes for bio-defence applications, C. Zhou, LLNL; J. Sirp, LLNL.

On the molecular quasispecies model and the dominance of the fittest genotype, T. Kostova, Page 134 of 276

National Science Foundation; C. Zhou, LLNL; A. Zemla, LLNL.

Understanding the Role of Quasispecies in Interspecies Transmission Events, M. K. Borucki, LLNL; J. E. Allen, LLNL; S. Messenger, Ca Dept Public Health; T. R. Slezak, LLNL.

Early and Rapid Detection of Ebola Hemorrhagic Fever Virus, A. Rosa, LLNL; C. Carrillo, LLNL; J. Thissen, LLNL; J. Olivas, LLNL; M. El Sheikh, LLNL; R. Lenhoff, LLNL; P. Naraghi-Arani, LLNL.

Detection of Intentional Food Contamination: Multiplexed Diagnostic Assays Applied to the Detection of Bio-threat Agents in Complex Matrices, A. Carrillo, LLNL; J. Olivas, LLNL; M. El Sheikh, LLNL; A. Rosa, LLNL; R. Lenhoff, LLNL; P. Naraghi-Arani, LLNL.

Chicken soup for the spore, L. Dugan, LLNL Characterization of Burkholderia isolates using genotyping microarrays, C. Jaing, LLNL.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: LLNL is performing work in the area of biological agent detection, therapeutics development, virulence mechanism elucidation, structural characterization, post- decontamination agent viability testing, response planning, and forensics. The biological detection platforms being developed at LLNL include multiplex assays, the Autonomous Pathogen Detection System (APDS), Biological Aerosol Mass Spectrometry (BAMS), Enhanced Biological Aerosol Detection System (EDBADS), and the Viral Discovery Platform (VDP). These platforms use PCR, immunoassay, mass spectrometry and genomic sequencing to gather useful information about the biological species present in the sampling environment. LLNL is also working to support and upgrade the biological detection network put in place by DHS known as BioWatch. Personnel from LLNL play an important role in the bioinformatics required to develop new detection assays for the various detection platforms. The development and screening of new DNA/RNA based assays is also a core area of expertise at LLNL. Testing and validation of new hardware components, and training for the BioWatch network is another area where LLNL supports the DHS mission. In addition to the detection platforms LLNL is also working on tools that will help restore normal activities in the event of a biological attack. These include developing rapid viability testing, decontamination strategies, and biological response plans for DHS, DOD, and EPA. We also have substantial activities in developing forensic assays to help determine where an agent may have come from and who might be responsible for the use of that agent. Beyond detection, response, recovery, and attribution LLNL also has ongoing research projects whose goal is to help elucidate the mechanism of host-pathogen interactions. The goal of this research is to understand how an organism is able to defeat or circumvent the host immune system. This will enable the development of new intervention strategies that are Page 135 of 276

specifically targeted to steps in the organism life cycle. LLNL is also involved in the search for new compounds that can be used as effective intervention strategies as well as the development of novel vaccine strategies for disease prevention. This work involves stimulating either innate or adaptive immunity for the prophylaxis and therapeutics.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A and B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 136 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Los Alamos National Laboratory (LANL)

2. Where is it located (provide both address and geographical location)?

Los Alamos National Laboratory P. O. Box 1663

Los Alamos, New Mexico 87545

3. Floor area of laboratory areas by containment level:

BL2 346 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 346 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 64

(ii) Division of personnel:

Military 0

Civilian 64

(iii) Division of personnel by category:

Scientists 27

Engineers 6

Technicians 28

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

automation Bacteriology Biochemistry Bioinformatics Biology Page 137 of 276

Biomedical Science Cell Biology Engineering Genomics Metagenomics, High Throughput Sequencing Microbiology Molecular Biology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Defense (DOD) - partly U.S. Department of Energy (DOE) U.S. Department of Health and Human Services (HHS) U.S. Department of Homeland Security (DHS) Internal (Laboratory Directed Research and Development LDRD) Other Governmental Agencies

(vii) What are the funding levels for the following program areas: Research $ 9,452,000 Development $ 5,393,000 Test and evaluation $ 8,840,000 Total $ 23,685,000

(viii) Briefly describe the publication policy of the facility: As a DOE/NNSA facility, LANL is required to make scientific and technical information broadly available, within applicable laws and Departmental requirements, to accomplish mission objectives and strategic goals, promote scientific advancement, satisfy statutory dissemination requirements, and ensure a fair return on Departmental and taxpayer investment.The Laboratory has a mandate to ensure that scientific and technical information is identified, processed, disseminated, and preserved to enable the scientific community and the public to locate and use the unclassified and unlimited-distribution information resulting from DOE research and related endeavors. The Laboratory also has procedures in place to manage and protect classified, sensitive controlled unclassified, and export-controlled scientific and technical information, yet make it accessible for appropriate access by the Page 138 of 276

Department, its contractors, and others.Reviews are conducted prior to publication to determine availability of information, or restrictions thereto. These reviews include, but are not limited to, the following: 1) classification/declassification, 2) copyrighted materials or other intellectual property, 3) export controls or distribution restrictions, and 4) sensitive content that limits access.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Hong-Geller, E. and Li, N. microRNAs as therapeutic targets to combat diverse human diseases In Drug Development/Book 2, 2011, ISBN 979-953-307-657-6.

Hong-Geller, E., Nowak-Lovato, KL, Micheva-Viteva, SN, and Lauer, SA. Regulation of host chemokine response by the pathogenic Type III secretion system, In Chemokines: Types, Functions, and Structural Characteristics, Keith J. Walker ed. 2011, Nova Publishers, Inc.

Shivakumara Siddaramappa, Jean F Challacombe, Jeannine M Petersen, Segaran Pillai, Geoff Hogg and Cheryl R Kuske. Common Ancestry and Novel Genetic Traits of Francisella novicida-Like Isolates from North America and Australia as Revealed by Comparative Genomic Analyses. 2011, Appl Environ Microbiol 77:5110-5122.

Macdonald, T. E, C. H. Hela, Y. Shou, Y. I. Valdez, L. O. Ticknor, B. T. foley, S. W. Davis, G. E. Hamilton, C. D. Kelly-Cirino, J. R. Barash, S. S. Arnon, M. Lindstrom, H. Korkeala, L. A. Smith, T. J. Smith and K.K. Hill. Analysis of Serotype E Strains using MLST, AFLP, VNTR and botulinum neurotoxin gene sequencing. Applied and Environmental Biology. Dec. 2011, 77(24) p8625-8634. Lee Borenstein, Alexander Roth, Rahul Oliver, Savanna L Carson, Tracy H Erkkila, Craig Blackheart, Jennifer Foster-Harris, Helen Cui, Chris Detter, Jeffrey Miller, and Hilary Godwin. Global Bio Lab: Enabling Technologies for High-Throughput Screening of Infectious Disease Samples" Abstract: LabAutomation 2011. Palm Springs, CA, January, 2011.

Zorayr Khalapyan, Alexander Roth, and Lee Borenstein. Automated Data Import and Validation Framework for a High-Throughput Laboratory. Abstract: LabAutomation 2011. Palm Springs, CA. January 2011.

Frank Masur, Alexander Roth, Lee Borenstein, and Craig Blackhart. Integration of Heterogeneous Automated Systems in a High Throughput Laboratory Using Web Services by the example of a LIMS and an Accessioning System. Abstract: LabAutomation 2011. Palm Springs, CA. January 2011.

Alexandra Weilharter, Birgit Mitter, Maria V. Shin, Patrick S. G. Chain, Jerzy Nowak, and Page 139 of 276

Angela Sessitsch, Complete genome sequence of the plant growth-promoting endophyte Burkholderia phytofirmans strain PsJN., J Bacteriol. 2011 Jul;193(13):3383-4. van Passel MW, Kant R, Palva A, Lucas S, Copeland A, Lapidus A, Glavina del Rio T, Dalin E, Tice H, Bruce D, Goodwin L, Pitluck S, Davenport KW, Sims D, Brettin TS, Detter JC, Han S, Larimer FW, Land ML, Hauser L, Kyrpides N, Ovchinnikova G, Richardson PP, de Vos WM, Smidt H, Zoetendal EG. Genome Sequence of Victivallis vadensis ATCC BAA-548, an Anaerobic Bacterium from the Phylum Lentisphaerae, Isolated from the Human Gastrointestinal Tract, J Bacteriol. 2011 May;193(9):2373-4.

Henry S. Gibbons, Stacey M. Broomall, Lauren A. McNew, Hajnalka Daligault, Carol Chapman, David Bruce, Mark Karavis, Michael Krepps, Paul A. McGregor, Charles Hong, Kyong H. Park, Arya Akmal, Andrew Feldman, Jeffrey S. Lin, Wenling E. Chang, Brandon W. Higgs, Plamen Demirev, John Lindquist, Alvin Liem, Ed Fochler, Timothy D. Read, Roxanne Tapia, Shannon Johnson, Kimberly A. Bishop-Lilly, Chris Detter, Cliff Han, Shanmuga Sozhamannan, C. Nicole Rosenzweig, Evan W. Skowronski, Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant, PLoS One. 2011 Mar 25;6(3):e17836.

Cale EM, Hraber P, Giorgi EE, Fischer W, Bhattacharya T, Leitner T, Yeh WW, Gleasner C, Green LD, Han CS, Korber B, Letvin NL. Epitope-Specific CD8(+) T Lymphocytes Cross-Recognize Mutant Simian Immunodeficiency Virus (SIV) Sequences but Fail To Contain Very Early Evolution and Eventual Fixation of Epitope Escape Mutations during SIV Infection, J Virol. 2011 Apr;85(8):3746-57.

Mark W. J. van Passel, Ravi Kant, Erwin G. Zoetendal, Caroline M. Plugge, Muriel Derrien, Stephanie A. Malfatti, Patrick S. G. Chain, Tanja Woyke, Airi Palva, Willem M. de Vos, Hauke Smidt, The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes., PLoS One. 2011 Mar 3;6(3):e16876.

Yang F, Zeng X, Ning K, Liu KL, Lo CC, Wang W, Chen J, Wang D, Huang R, Chang X, Chain PS, Xie G, Ling J, Xu J. Saliva microbiomes distinguish caries-active from healthy human populations, ISME J. 2011 Jun 30. doi: 10.1038/ismej.2011.71.

Harris, J. F., Erkkila, T., Blackhart, C., Randow, M., Gleasner, C., Green, L., Cash, L., Schmidt, J. G., McMahon, B., Yeghiazarian, L., Marrone, B., Cui, H., Roth, A., Borenstein, L., Godwin, H., Beugelsdijk, T., Layne, S., and Detter, J. C. (2011) Design of an automated laboratory for high-throughput influenza surveillance, Influenza Other Respiratory Viruses, 2011 May; 5(1):423-424.

N. Dover, J. R. Barash, K. K. Hill, J. C. Detter and S. S. Arnon, Novel Structural Elements within the Nonproteolytic Clostridium botulinum Type F Toxin Gene Cluster, Appl Environ Microbiol. 2011 Mar;77(5):1904-6.

Page 140 of 276

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The biological defense research at the Los Alamos National Laboratory includes the following areas: pathogen signature identification, host-pathogen interaction characterization, biothreat agent virulence study, and pathogen detection technology development. The main objectives for these research and development activities are to: understand molecular mechanisms of host-pathogen interaction, study molecular, chemical, and physical signatures of biothreat agents for pathogen detection and characterization; study microbial organism genetic variations for detection assay design and improvement; evaluate detection assay and platform performance; improve sample collection techniques; develop environmental sample analysis and pathogen fate analysis techniques; develop DNA, RNA and protein based detection and bioforensics assays; develop next generation high throughput microbial sequencing and finishing capabilities; develop high throughput assays for host-pathogen protein interactions screening; and identify host molecular targets as potential therapeutic candidates.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins Including NIAID Category B Priority Pathogens

• USDA Plant Protection and Quarantine (PPQ) Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 141 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Pacific Northwest National Laboratory (PNNL)

2. Where is it located (provide both address and geographical location)?

Pacific Northwest National Laboratory P. O. Box 999

Richland, Washington 99352

3. Floor area of laboratory areas by containment level:

BL2 875 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 875 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 30

(ii) Division of personnel:

Military 0

Civilian 30

(iii) Division of personnel by category:

Scientists 27

Engineers 0

Technicians 0

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Analytical Biochemistry Analytical Chemistry Analytical Mass Spectrometry Bacteriology Biochemistry Page 142 of 276

Bioenvironmental Engineering Bioinformatics Biology Biophysics Biotechnology Cell Biology Chemistry Computational Biology Engineering Environmental Engineering Environmental Science Food and Water Testing Genomics Infectious Disease Mass Spectrometry Mass Spectrometry Biochemistry Microbial Forensics Microbiology Molecular Biology Parasitology Pathogenesis Protein Chemistry Proteomics Public Health Statistics Structural Biology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

(vii) What are the funding levels for the following program areas: Research $ 15,368,000 Development $ 0 Test and evaluation $ 0 Total $ 15,368,000

(viii) Briefly describe the publication policy of the facility: PNNL encourages its staff to publish the results of their work in the peer-reviewed literature. Prior to being released from the laboratory, each document must undergo internal peer-review, review by a technical editor and line management to assure that the document is well-written and contains original material. In addition, each document is checked to make sure it contains no information that could affect national security or information that might require intellectual property protection or an export control license.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Smallwood, H.S., D. Lopez-Ferrer, and T.C. Squier. 2011. Aging enhances production of reactive oxygen species and bactericidal activity in peritoneal macrophages by up-regulating classical activation pathways. Biochemistry 50, 9911-9922.

Xiong, Y., B. Chen, L. Shi, J. K. Fredrickson, D. J. Bigelow, and T. C. Squier. 2011. Targeted protein degradation of outer membrane decaheme cytochrome MtrC metal reductase in Shewanella oneidensis MR-1 measured using biarsenical probe CrAsH-EDT2. Biochemistry 50, 9738-9751.

Shi, L.,S. M. Belchik, A. E. Plymale, S. Heald, A. C. Dohnalkova, K. Sybirna, H. Bottin, T. C. Squier, J. M. Zachara, and J. K. Fredrickson. 2011. Purification and Characterization of [NiFe]-Hydrogenase of Shewanella oneidensis MR-1. Appl. Environ. Microbiol, 77, 5584- 5590. Bigelow, D.J., and T. C. Squier. 2011. Redox regulation of cellular signaling and stress response through reversible oxidation of methionines in calmodulin. Molecular Biosystems 7, 2101-2109.

Hou, C., Y. Xiong, N. Fu, C. C. Jacquot, T. C. Squier, and H. Cao. 2011. Turn-on ratiometric fluorescent sensor for Pb2+ detection. Tetrahedron Lett., 52, 2692-2696. Determination of Post-Culture Processing with Carbohydrates by MALDI-MS and TMS derivatization GC/MS.

Wunschel DS, KL Wahl, AM Melville, CM Sorensen, HA Colburn, NB Valentine, and CL Stamper. 2011. "Determination of Post-Culture Processing with Carbohydrates by MALDI- Page 144 of 276

MS and TMS derivatization GC/MS." Talanta 85(5):2352-2360. doi:10.1016/j.talanta.2011.07.073

Integration of Gas Chromatography Mass Spectrometry Methods for Differentiating Ricin Preparation Methods Wunschel DS, AM Melville, CJ Ehrhardt, HA Colburn, KD Victry, KC Antolick, JH Wahl, and KL Wahl. 2011. "Integration of Gas Chromatography Mass Spectrometry Methods for Differentiating Ricin Preparation Methods." PNNL-SA-82375, Pacific Northwest National Laboratory, Richland, WA. [Unpublished]

Salmonella-secreted Virulence Factors Heffron F, G Niemann, H Yoon, AS Kidwai, RN Brown, JE McDermott, RD Smith, and JN Adkins. 2011. "Salmonella-secreted Virulence Factors." Chapter 10 in Salmonella: From Genome to Function, ed. S Porwollik, pp. 187- 223. Caister Academic Press, Norfolk, United Kingdom.

Discovery of Salmonella Virulence Factors Translocated via Outer Membrane Vesicles to Murine Macrophages. Yoon H, C Ansong, JN Adkins, and F Heffron. 2011. "Discovery of Salmonella Virulence Factors Translocated via Outer Membrane Vesicles to Murine Macrophages." Infection and Immunity 79(6):2182-92. doi:10.1128/IAI.01277-10.

Discovery of Novel Secreted Virulence Factors from Salmonella enterica Serovar Typhimurium by Proteomic Analysis of Culture Supernatants Niemann G, RN Brown, JK Gustin, A Stufkens, AS Shaikh-Kidwai, J Li, JE McDermott, HM Brewer, AA Schepmoes, RD Smith, JN Adkins, and F Heffron. 2011. "Discovery of Novel Secreted Virulence Factors from Salmonella enterica Serovar Typhimurium by Proteomic Analysis of Culture Supernatants." Infection and Immunity 79(1):33-43. doi:10.1128/IAI.00771-10.

Computational prediction of type III and IV secreted effectors in Gram-negative bacteria McDermott JE, AL Corrigan, ES Peterson, CS Oehmen, G Niemann, E Cambronne, D Sharp, JN Adkins, R Samudrala, and F Heffron. 2011. "Computational prediction of type III and IV secreted effectors in Gram-negative bacteria ." Infection and Immunity 79(1):23-32. doi:10.1128/IAI.00537-10.

A multi-pronged search for a common structural motif in the secretion signal of Salmonella enterica serovar Typhimurium type III effector proteins Buchko GW, G Niemann, ES Baker, ME Belov, RD Smith, F Heffron, JN Adkins, and JE McDermott. 2010. "A multi- pronged search for a common structural motif in the secretion signal of Salmonella enterica serovar Typhimurium type III effector proteins." Molecular Biosystems 6(12):2448-2458. doi:10.1039/c0mb00097c.

A Three-way Comparative Genomic Analysis of Mannheimia haemolytica Isolates Lawrence P, W Kittichotirat, JE McDermott, and RE Bumgarner. 2010. "A Three-way Comparative Genomic Analysis of Mannheimia haemolytica Isolates." BMC Genomics 11:535. doi:10.1186/1471-2164-11-535.

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Page 145 of 276

Research Paradigm Aderem A, JN Adkins, C Ansong, J Galagan, S Kaiser, MJ Korth, GL Law, JE McDermott, S Proll, C Rosenberger, G Schoolnik, and MG Katze. 2011. "A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm." mBio 2(1):Article No. e00325. doi:10.1128/mBio.00325-10.

Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium Ansong C, N Tolic, SO Purvine, S Porwollik, MB Jones, H Yoon, SH Payne, JL Martin, MC Burnet, ME Monroe, P Venepally, RD Smith, S Peterson, F Heffron, M Mcclelland, and JN Adkins. 2011. "Experimental annotation of post- translational features and translated coding regions in the pathogen Salmonella Typhimurium." BMC Genomics 12:Art. No. 433. doi:10.1186/1471-2164-12-433.

Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella Yoon H, C Ansong, JE McDermott, MA Gritsenko, RD Smith, F Heffron, and JN Adkins. 2011. "Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella ." BMC Systems Biology 5:Article No. 100. doi:10.1186/1752-0509-5-100.

A community effort towards a knowledge-Â¬base and mathematical model of the human pathogen Salmonella Typhimurium LT2 Thiele I, DR Hyduke, B Steeb, G Fankam, DK Allen, S Bazzani, P Charusanti, FC Chen, RM Fleming, CA Hsiung, SC De Keersmaecker, YC Liao, K Marchal, ML Mo, E Ozdemir, A Raghunathan, JL Reed, SI Shin, S Sigurbjornsdottir, J Steinmann, S Sudarsan, N Swainston, IM Thijs, K Zengler, BO Palsson, JN Adkins, and D Bumann. 2011. "A community effort towards a knowledge-Â¬base and mathematical model of the human pathogen Salmonella Typhimurium LT2 ." BMC Systems Biology 5:Article No. 8. doi:10.1186/1752-0509-5-8.

Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella. McDermott JE, H Yoon, ES Nakayasu, TO Metz, DR Hyduke, AS Kidwai, BO Palsson, JN Adkins, and F Heffron. 2011. "Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella." Frontiers in Microbiology 2:121. doi:10.3389/fmicb.2011.00121.

Zhang Y, Buchko GW, Qin L, Robinson H, Varnum SM (2011). Crystal structure of the receptor binding domain of the botulinum D-D mosaic neurotoxin reveals potential roles of lysines 1118 and 1136 in membrane interactions. Biochem Biophys Res Commun. 404(1):407-412. Zhang Y, Varnum SM (2012) The receptor binding domain of botulinum neurotoxin serotype C binds phosphoinositides. Biochimie, 94: 920-923.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The primary objectives of the projects listed in this report include: Developing tools for Page 146 of 276

organic signatures characterization in biological materials for forensic attribution. This generically includes both volatile and non-volatile organic components as either direct or indirect signatures of the culture media, preparation conditions, or treatment processes. Investigation of nucleic acid and immunoassay detection methods for biological threat agents and to be able to discriminate from non-pathogenic near neighbors. DNAs and BSL1/BSL2 whole organisms from Bacillus spp. Francisella sp.and Yersinia spp are used in this research. Investigating methods for detection and determination of food and waterborne pathogens. Microorganisms include muirine norovirus, human norovirus, Listeria monocytogenes. We check for human papilloma virus because the HeLa cell line is used for cultivating human noroviruses. Understanding mechanisms in natural protein scaffolds underlying molecular recognition of diverse families of analytes to allow rapid molecular engineering of affinity reagents capable of threat detection. Developing diagnostic assays for toxin detection and activity, including a platform for toxin detection based upon a combination of 2 analytical approaches: 1) molecular recognition and 2) enzymatic activity assays. Using mass spectrometry methods to elucidate functional changes in the proteomes of infectious bacteria under relevant growth conditions, host-derived cell-lines during infection, or with over-expressed pathogen secreted proteins. Applying synthetic biology/genetic engineering tools to design and build a living cellular sensor that can be tuned to respond to selectable targets. Characterizing the ability of biofilms to capture,retain, or respond to a variety of contaminants. The objective of the LDRD effort, is to investigate stable platforms for novel molecular recognition elements for pathogen detection. The team is using mass spectrometry methods to elucidate functional changes in the proteomes of infectious bacteria under relevant growth conditions, host-derived cell-lines during infection, or with over-expressed pathogen secreted proteins.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 147 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Sandia National Laboratories (SNL)

2. Where is it located (provide both address and geographical location)?

Sandia National Laboratories P. O. Box 5800

Albuquerque, New Mexico 87185

3. Floor area of laboratory areas by containment level:

BL2 1293 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 1293 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 85

(ii) Division of personnel:

Military 0

Civilian 85

(iii) Division of personnel by category:

Scientists 41

Engineers 10

Technicians 33

Administrative and support staff 1

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Aerosol Science Analytical Biochemistry Analytical Chemistry Analytical Mass Spectrometry Bacteriology Page 148 of 276

Biochemistry Bioengineering Biofuel Production Bioinformatics Bioinorganic Chemistry Biology Biomedical Engineering Biomedical Science Biophysics Biotechnology Cell Biology Chemical Engineering Chemistry Computational Biology Electrical Engineering Engineering Environmental Science Genetics Genomics Geosciences Health Science High Throughput Sequencing imaging & microscopy Immunology Infectious Disease Mass Spectrometry Mass Spectrometry Biochemistry Materials Science Microbiology Microfluidics Molecular Biology Molecular Computational Biology Molecular Pathogenic Microbiology Molecular Spectroscopy and Imaging Molecular Toxicology Nanotechnology Neuroscience Optical Spectroscopy Pathogenesis Pathology Pharmacology Phycology, Mycology Physics Physiology Plant Physiology Page 149 of 276

Protein Chemistry Protein Engineering Proteomics Structural Biology Systems Biology Toxicology Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 16

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

(vii) What are the funding levels for the following program areas: Research $ 48,311,000 Development $ 832,000 Test and evaluation $ 217,000 Total $ 49,360,000

(viii) Briefly describe the publication policy of the facility: Scientists are encouraged to publish their results in the peer-reviewed scientific literature as well as present their work at national and international professional meetings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Liu, H., and Bachand, G.D.; Understanding energy dissipation and thermodynamics in biomotor-driven nanocomposite assemblies. Soft Matter 7(6): 3087-3091 Comparative genomic analysis of the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris (VOLUME 29, NUMBER 10, OCTOBER 2011, NATURE Page 150 of 276

BIOTECHNOLOGY).

Khripin, C. Y.; Pristinski, D.; Dunphy, D. R.; Brinker, C. J.; Kaehr, B. J. Protein-Directed Assembly of Arbitrary Three-Dimensional Nanoporous Silica Architectures. ACS Nano. 2011, 5, 1401-1409.

Jiang, X.; JIang, Y.; Liu, N.; Xu, H. F.; Rathod, S.; Shah, P.; Brinker, C. J. Controlled Release from Core-Shell Nanoporous Silica Particles for Corrosion Inhibition of Aluminum Alloys. Journal of Nanomaterials. 2011, 2011, 760237+.

Harper, J. C.; Lopez, D. M.; Larkin, E. C.; Economides, M. K.; McIntyre, S. K.; Alam, T. M.; Tartis, M. S.; Werner-Washburne, M.; Brinker, C. J.; Brozik, S. M.; Wheeler, D. R. Encapsulation of S. Cerevisiae in Poly(Glycerol) Silicate Derived Matrices: Effect of Matrix Additives and Cell Metabolic Phase on Long-Term Viability and Rate of Gene Expression. Chemistry of Materials. 2011, 23, 2555-2564.

Baca, H. K.; Carnes, E. C.; Ashley, C. E.; Lopez, D. M.; Douthit, C.; Karlin, S.; Brinker, C. J. Cell-Directed-Assembly: Directing the Formation of Nano/Bio Interfaces and Architectures with Living Cells. Biochimica et Biophysica Acta (BBA) - General Subjects. 2011, 1810, 259-267.

Collins, AM, Jones, HDT, Han, D, Hu, Q, Beechem, TE, and Timlin, JA "Carotenoid Distribution in Living Cells of Haematococcus pluvialis (Chlorophyceae)," PLoS One, 2011, 6:9, e24302.

Aaron, JS, Greene, A Kotula, PG, Bachand,GD, and Timlin, JA. "Advanced Optical Imaging Reveals Dependence of Particle Geometry on Interactions between CdSe Quantum Dots and Immune Cells." Small, 2011, 7:3, 334-341.

T. Oprea, E. May, A. Leitao, A. Tropsha. Computational Systems Chemical Biology, Methods Mol Biol.; 672:459-88, 2011. E. May. Circuit-based Models of Biomolecular System Dynamics. In Simulation and Verificationof Electronic and Biological Systems. 2011.

E. May. Investigating the metabolic dynamics of pathogenic organisms using BioXyce. Proceedings of the IEEE Engineering in Medicine and Biology Society International Conference, September 2011. Invited.

E. May. Theoretical modeling and analysis of oxygen availability and metabolic dynamics of Mycobacterium tuberculosis. Keystone Symposium on Tuberculosis: Biology, Pathology and Therapy. Jan. 2011.

Bharadwaj, R. A.; Wong B. Knierim; S. Singh; B.M. Holmes; M. Auer; B.A. Simmons; P.D. Adams and A.K. Singh, "High-Throughput Enzymatic Hydrolysis of Lignocellulosic Page 151 of 276

Biomass via In-Situ Regeneration," Bioresource Technology, 102, 1329-1337, 2011.

Gillespie JJ, Joardar V, Williams KP, Driscoll T, Hostetler JB, Nordberg E, Shukla M, Wallenz B, Hill CA, Nene VM, Azad AF, Sobral BW, Caler E., "A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of obligate intracellular lifestyle," J Bacteriol 194: 376-94 (2011).

Verhoef L, Williams KP, Kroneman A, Sobral B, van Pelt W, Koopmans M., "Selection of a phylogenetically informative region of the norovirus genome for outbreak linkage," Virus Genes: Epub ahead of print (2011)

Gillespie, JJ, et al. (25 authors), "PATRIC: the comprehensive bacterial bioinformatics resource with a focus on human pathogenic species," Infect Immun 79:4286-98. (2011).

Bateman A, et al. (30 authors), "RNAcentral: a vision for an international database of RNA sequences," RNA 17:1941-6. (2011) Shulaev V, et al. (71 authors), "The genome of woodland strawberry (Fragaria vesca)," Nat Genet 43:109-16. (2011) Gil,

G.-C., Brennan, J., Throckmorton, D., Branda, S., Chirica, G., "Automated analysis of serum peptidome using restricted access media and nanoliquid chromatography-tandem mass spectrometry. J. Chromatogr." B 2011, 879, 1112-1120. (2011).

Zendejas, F.J., Benke, P., Lane, P.D., Simmons, B.A. and Lane, T.W. 2012. "Characterization of Biodiesel Derived from Vegetable, and Microalgae (Thalassiosira pseudonana and Phaeodactylum tricornutum) Triacylglycerols," Biotechnol. Bioeng. In Press. (2011).

Van Benthem, M.H., Lane, T.W., Davis, R.W., Lane P. D., and Keenan M.R., 2011. "PARAFAC Modeling of Three-Way Hyperspectral Images: Endogenous Fluorophores as Health Biomarkers in Aquatic Species," Chemomet. Intel. Lab. Sys 106:115-124 (2011).

Ulrich Y. Schaff and Greg J. Sommer. "Rapid Whole Blood Immunoassay Based on Centrifugal Bead Sedimentation" Clinical Chemistry, 57, 753-761 (2011).

Greg J. Sommer, Junyu Mai, Anup K. Singh, and Anson V. Hatch. "Microscale Isoelectric Fractionation Using Photopolymerized Membranes," Analytical Chemistry, 83, 3120-3125 (2011).

Zendejas, F. J.; Meagher, R. J.; Stachowiak, J. C.; Hayden, C. C.; Sasaki, D. Y. "Orientation of Lipid Domains in Giant Vesicles Using an Electric Field," ChemComm 47(26), 7320 - 7322 (2011).

Stachowiak, J. C.; Hayden, C. C.; Sanchez, M. A. A.; Wang, J.; Bunker, B. C.; Voigt, J. A.; Sasaki, D. Y. "Targeting Proteins to Liquid-Ordered Domains in Lipid Membranes," Page 152 of 276

Langmuir 27, 1457-1462 (2011).

C.E. Ashley, D.R. Dunphy, J. Zhang, E.C. Carnes, Z. Yuan, D.N. Petsev, P. Atanassov, O.D. Velev, M. Sprung, J. Wang, C. J. Brinker, and D.S. Peabody, "Convective Assembly of 2D Lattices of Virus-Like Particles Visualized by In-situ Grazing Incidence Small-Angle Scattering," SMALL 7 (8) 1043-1050, Apr 2011.

C.E. Ashley, E.C. Carnes, G.K. Phillips, D. Padilla, P.N. Durfee, P.A. Brown, T. N. Hanna, J. Liu, B. Phillips, M.B. Carter, N.J. Carroll, X. Jiang, D.R. Dunphy, C.L. Willman, D.N. Petsev, D.G. Evans, A.N. Parikh, B. Chackerian, W Wharton, D.S. Peabody, and C.J. Brinker, "The Targeted Delivery of Multicomponent Cargos to Cancer Cells via Nanoporous Particle-Supported Lipid Bilayers," Nature Materials, 10 (5) 389-397, May 2011 (COVER).

C.E. Ashley, EC Carnes, GK Phillips, PN Durfee, MD Buley, CA Lino, DP Padilla, B. Phillips, MB Carter, CL: Willman, CJ Brinker, J do Carmo Caldeira, B. Chackerian, W. Wharton and DS Peabody. "Cell-Specific Delivery of Diverse Cargos by Bacteriophage MS2 Virus-Like Particles," ACS Nano, 5 (7) 5729-5745, July 2011 (COVER).

P. Liu, R. J. Meagher, Y. K. Light, S. Yilmaz, R. Chakraborty, A. P. Arkin, T. C. Hazen, A. K. Singh, "Microfluidic fluorescence in situ hybridization and flow cytometry (ÂµFlowFISH)," Lab on a Chip, 11, 2673-2679 (2011).

S. Pushalkar, S. P. Mane, X. Ji, Y. Li, C. Evans, O. R. Crasta, D. Morse, R. Meagher, A. Singh, and D. Saxena,"Microbial diversity in saliva of oral squamous cell carcinoma," FEMS Immunology & Medical Microbiology, 61, 269-277 (2011).

Yilmaz S, Singh AK., "Single cell genome sequencing," Current Opinion in Biotechnology, DOI: 10.1016/j.copbio.2011.11.018 (2011) Wu, Huawen; Volponi, Joanne V.; Oliver, Ann E.; Parikh, Atul N.; Simmons, Blake A.; Singh, Seema. "In vivo lipidomics using single-cell raman spectroscopy." Proceedings of the National Academy of Sciences of the United States of America (2011), 108(9), 3809-3814

Reindl, W.; Deng, K.; Gladden, J.M.; Cheng, G.; Wong, A.; Singer, S.W.; Singh, S.; Lee, J.- C.; Yao, C.-H.; Hazen, T.C.; Singh, A.K.; Simmons, B.A.; Adams, P.D.; Northen, T.R. "Colloid-based multiplexed screening for plant biomass-degrading glycoside hydrolase activities in microbial communities," Energy and Environmental Science, 2011, DOI: 10.1039/C1EE01112J

Kim, Hanyoup; Bartsch, Michael S.; Renzi, Ronald F.; He, Jim; Van de Vreugde, James L.; Claudnic, Mark R.; and Patel, Kamlesh D. "Automated Digital Microfluidic Sample Preparation for Next-Generation DNA Sequencing," Journal of Laboratory Automation 2011 16:405

Wu, M.and Singh A.K. "Single cell protein analysis," Current Opinion in Biotechnology Page 153 of 276

2011 23 1-6.

Greene, A.C., Washburn, C.M., Bachand, G.D., James, C.D., "Combined chemical and topographical guidance cues for directing cytoarchitectural polarization in dissociated primary neurons," Biomaterials 2011; 32, pp. 8860-8869. "Critical Conditions for Ferric Chloride Induced Flocculation of Freshwater Algae," BIOTECHNOLOGY AND BIOENGINEERING Volume: 109 Issue: 2 Pages: 493-501 DOI: 10.1002/bit.23319 Published: FEB 2012.

Altman, S. J., M. Hibbs, P. B. Savage, H. D. T. Jones, S. Branda, L. K, McGrath, Y. Feng, M. F. Kirk, J. Pollard, A. Lichtenberger, C. Marry, S. Stafslien, D. Goeres and K. Buckingham-Meyer, Linking Ceragenins to Water-Treatment Membranes to Minimize Biofouling, SAND2012- 0181, Sandia National Laboratories, Albuquerque, NM, 2012.

Altman, S. J., R. P. Jensen, M. A. Cappelle, A. L. Sanchez, R. L. Everett, H. L. Anderson, Jr., and L. K. McGrath, Membrane Treatment of Side-Stream Cooling Tower Water for Reduction of Water Usage, Desalination, 285, 177-183, 2012.

Kirk, M. F. (2011), Variation in Energy Available to Populations of Subsurface Anaerobes in Response to Geological Carbon Storage, Environmental Science & Technology, 45(15), 6676-6682.

Cheng, G., et al, "Neutron reflectometry and QCM-D study of the interaction of cellulases with films of amorphous cellulose", Biomacromolecules 2011, 12, 2216 – 2224.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The Sandia Chem/Bio program is an applied research program designed to develop and demonstrate technologies and systems that can be used to mitigate the impact of attacks on civilian populations with chemical or biological agents. Specific aims include: a. Analyze pathogenic mechanisms caused by toxins interacting with cell membranes; b. Development of diagnostic and detection technologies for toxins, bacteria, and viruses by applying micro- separations technology; c. Development of technologies for the characterization of aerosolized particles using optics, among many others. Work with biological agents at Sandia also includes work in nanotechnology and biofuels.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Page 154 of 276

Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None.

Page 155 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, National Center for Environmental Health (NCEH), Division of Laboratory Sciences (DLS)

2. Where is it located (provide both address and geographical location)?

Centers for Disease Control and Prevention, U.S. Department of Health and Human Services 4770 Buford Highway Mail stop F-47 Atlanta, Georgia 30341

3. Floor area of laboratory areas by containment level:

BL2 0 (sqM) BL3 114 (sqM) BL4 0 (sqM) Total laboratory floor area 114 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 10

(ii) Division of personnel:

Military 0

Civilian 10

(iii) Division of personnel by category:

Scientists 10

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biochemistry Biology Chemistry Page 156 of 276

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 3

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC)

(vii) What are the funding levels for the following program areas: Research $ 1,136,260 Development $ 0 Test and evaluation $ 757,506 Total $ 1,893,766

(viii) Briefly describe the publication policy of the facility: Scientists are encouraged to publish their results in the peer reviewed scientific literature as well as present their work at national and international professional meetings.

The clearance policy for information products disseminated outside CDC for public use is available online at: http://www.cdc.gov/od/science/policies

CDC Policy on "Oversight and clearance of dual use research of concern," is available online at:http://aops-mas-iis.cdc.gov/Policy/Doc/policy516.pdf

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

1. S.R. Kalb, J. Baudys, C. Egan, T. J. Smith, L.A. Smith, J.L. Pirkle, and J.R. Barr, Clostridium Baratii Type F Neurotoxin CLeaves Synaptobrevin-2 with Different Substrate Recognition Requirement than Clostridium botulinum Type F Neurotoxin, Applied and Environmental Microbiology, 2011, 77, 1301-1308. 2. H. Moura, R.R. Terilli, A.R. Woolfitt, M. Gallegos-Candela, L.G. McWilliams, M.I. Solano, J.L. Pirkle, and J.R. Barr, Studies on botulinum neurotoxins type /C1 and mosaic/DC using Endopep-MS and protemics, FEMS Immunol Med Microbiol, 2011, 61(3), 288-300. 3. D. Wang, J. Baudys, S.R. Kalb, and J.R. Barr, Improved Detection of Botulinum Neurotoxin Type A in Stool by Mass Spectrometry, Analytical Biochemistry, 2011, 412, 67-73. 4. A. Boyer, M. Gallegos-Candela, R. Lina, Z. Kuklenyik, A. Woolfitt, H. Moura, S. Page 157 of 276

Kalb, C. Quinn, and J. Barr, Quantitative Mass Spectrometry for Bacterial Protein Toxins - Sensitive, Specific, High-Throughput Tool for Detection and Diagnosis, Molecules, 2011, 16(3), 2391-413. 5. S.C. McGrath, D.M. Schieltz, L.G. McWilliams, J.L. Pirkle, and J.R. Barr, Detection and quantification of ricin in beverages using isotope dilution tandem mass spectrometry, Anal Chem, 2011, 83(8), 2897-905. 6. S.A. Gray, J.R. Barr, S.R. Kalb, J.D. Marks, C.L. Baird, G.A. Cangelosi, K.D. Miller, and M.J. Feldhaus, Synergistic Capture of Clostridium botulinum Type A neurotoxin by scFv antibodies to novel epitopes, Biotechnology and Bioengineering, 2011, 108(10), 2456-2467. 7. D.M. Schieltz, S.C. McGrath, L.G. McWilliams, J. Rees, M.D. Bowen, J.J. Kools, L.A. Dauphin, E. Gomez-Saladin, B.N. Newton, H.L. Stang, M.J. Vick, J. Thomas, J.L. Pirkle, and J.R. Barr, Analysis of active ricin and castor bean proteins in a ricin preparation, castor bean extract, and surface swabs from a public health investigation, Forensic Sci Int, 2011, 209(1-3), 70-9. 8. M. Hedeland, H. Moura, V. Baverud, A.R. Woolfitt, U. Bondesson, and J.R. Barr, Confirmation of botulism in birds and cattle by the mouse bioassay and Endopep- MS, J Med Microbiol, 2011, 60, 1299-305. 9. R.R. Terilli, H. Moura, A.R. Woolfitt, J. Rees, D.M. Schieltz, and J.R. Barr. A historical and proteomic analysis of botulinum neurotoxin type/G, BMC Microbiology, 2011, 11, 232. 10. S.R. Kalb, W.I. Santana, I.N. Geren, C. Garcia-Rodriguez, J. Lou, T.J. Smith, J.D. Marks, L.A. Smith, J.L. Pirkle, and J.R. Barr, Extraction and inhibition of enzymatic activity of botulinum neurotoxins/B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies, BMC Biochemistry, 2011, 12(58), 1-12. 11. B.A. Parks, J.D. Shearer, J. Baudys, S.R. Kalb, D.C. Sanford, J.L. Pirkle, and J.R. Barr, Quantification of Botulinum Neurotoxin Serotypes A and B from Serum using Mass Spectrometry, Analytical Chemistry, 2011, 83(23), 9047-9053. 12. S.R. Kalb, J. Baudys, R.P. Webb, P. Wright, T.J. Smith, L.A. Smith, R. Fernandez, B.H. Raphael, S.E. Maslanka, J.L. Pirkle, and J.R. Barr, Discovery of a Novel Enzymatic Cleavage Site for Botulinum Neurotoxin F5, FEBS Letters, 2012, 586(2), 109-115.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The CDC National Center for Environmental Health, Division of Laboratory Science has successfully developed toxin assays that are critical for better detection and diagnosis during a public health response to biological toxins.

(ii) Agents Microorganisms and/or Toxins: Page 158 of 276

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

(iii) Outdoor Studies: None

Page 159 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, Office of Infectious Diseases (OID)

2. Where is it located (provide both address and geographical location)?

Atlanta, GA 1600 Clifton Road N.E.

Atlanta, Georgia 30333

3. Floor area of laboratory areas by containment level:

BL2 294 (sqM) BL3 2325 (sqM) BL4 543 (sqM) Total laboratory floor area 3162 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 238

(ii) Division of personnel:

Military 0

Civilian 238

(iii) Division of personnel by category:

Scientists 206

Engineers 0

Technicians 30

Administrative and support staff 2

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology Epidemiology Microbiology Molecular Biology Public Health Page 160 of 276

Statistics Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 40

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC) Internal (Laboratory Directed Research and Development LDRD) U.S. Department of Homeland Security (DHS) U.S. Department of Defense (DOD) - partly U.S. Environmental Protection Agency (EPA) U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas: Research $ 12,814,857 Development $ 3,121,248 Test and evaluation $ 4,072,632 Total $ 20,008,737

(viii) Briefly describe the publication policy of the facility: Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Agency.

The clearance policy for information products disseminated outside CDC for public use is available online at: http://www.cdc.gov/od/science/policies

CDC Policy on "Oversight and clearance of dual use research of concern" is available online at: http://aops-mas-iis.cdc.gov/Policy/Doc/policy516.pdf

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Albarino, Cesar G.; Bird, Brian H.; Chakrabarti, Ayan K.; Dodd, Kimberly A.; Erickson, Bobbie Ray, and Nichol, Stuart T. Efficient rescue of recombinant Lassa virus reveals the influence of S segment noncoding regions on virus replication and virulence. Journal of Page 161 of 276

Virology. 2011; 85(8):4020-4024.

Albarino, Cesar G.; Bird, Brian H.; Chakrabarti, Ayan K.; Dodd, Kimberly A.; Flint, Michael; Bergeron, Eric; White, David M., and Nichol, Stuart T. The major determinant of attenuation in mice of the Candid1 vaccine for Argentine hemorrhagic fever is located in the G2 glycoprotein transmembrane domain. Journal of Virology. 2011; 85(19):10404-10408.

Albarino, Cesar G.; Bird, Brian H.; Chakrabarti, Ayan K.; Dodd, Kimberly A.; White, David M.; Bergeron, Eric; Shrivastava-Ranjan, Punya, and Nichol, Stuart. T. Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains. Journal of Virology. 2011; 85(1):112-122.

Andriamandimby, Soa Fy; Marianneau, Philippe; Rafisandratantsoa, Jean-Theophile; Rollin, Pierre E.; Heraud, Jean-Michel; Tordo, Noel, and Reynes, Jean-Marc. Crimean-Congo hemorrhagic fever serosurvey in at-risk professionals, Madagascar, 2008 and 2009. Journal of Clinical Virology. 2011; 52(4):370-372.

Aradaib, Imadeldin E.; Erickson, Bobbie R.; Karsany, Mubarak S.; Khristova, Marina L.; Elageb, Rehab M.; Mohamed, Mohamed E., and Nichol, Stuart T. Multiple crimean-congo hemorrhagic Fever virus strains are associated with disease outbreaks in Sudan, 2008-2009. PLoS Neglected Tropical Diseases. 2011; 5(5):e1159.

Beeler E., K.F. Abramowicz, M.L. Zambrano, M.M. Sturgeon, N. Khalaf, R. Hu, G.A. Dasch, and M.E. Eremeeva. 2011. A focus of dogs and Rickettsia massiliae-infected Rhipicephalus sanguineus in California. Am. J. Trop. Med. Hyg. 84(2):244-249.

Boyer AE, Quinn CP, Beesley CA, Gallegos-Candela M, Marston CK, Cronin LX, Lins RC, Stoddard RA, Li H, Schiffer J, Hossain MJ, Chakraborty A, Rahman M, Luby SP, Shieh W, Zaki S, Barr JR, Hoffmaster AR. Lethal Factor Toxemia and Anti-Protective Antigen Antibody Activity in Naturally Acquired Cutaneous Anthrax. J Infect Dis. 2011: 204(9):1321-7.

Bird, Brian H.; Maartens, Louis H.; Campbell, Shelley; Erasmus, Baltus J.; Erickson, Bobbie R.; Dodd, Kimberly A.; Spiropoulou, Christina F.; Cannon, Deborah; Drew, Clifton P.; Knust, Barbara; McElroy, Anita K.; Khristova, Marina L.; Albarino, Cesar G., and Nichol, Stuart T. Rift Valley Fever Virus Vaccine Lacking the NSs and NSm Genes Is Safe, Nonteratogenic, and Confers Protection from Viremia, Pyrexia, and Abortion following Challenge in Adult and Pregnant Sheep. Journal of Virology. 2011; 85(24):12901-12909.

Calisher, Charles H.; Mills, James N.; Root, J. Jeffrey; Doty, Jeffrey B., and Beaty, Barry J. The relative abundance of deer mice with antibody to Sin Nombre virus corresponds to the occurrence of hantavirus pulmonary syndrome in nearby humans. Vector Borne and Zoonotic Diseases. 2011; 11(5):577-582. Page 162 of 276

DS, Emerson GL, Li Y, Sammons S, Olson V, Frace M, Nakazawa Y, Czerny Tand M, Kolodziejek J, Nowotny N, Olsen-Rasmussen M, Khristova M, Govil D, 2011;6(8):e23086.

Carroll, Serena A.; Reynes, Jean-Marc; Khristova, Marina L.; Andriamandimby, Soa Fy; Rollin, Pierre E., and Nichol, Stuart T. Genetic evidence for Rift Valley fever outbreaks in Madagascar resulting from virus introductions from the East African mainland rather than enzootic maintenance. Journal of Virology. 2011; 85(13):6162-6167.

Carver, Scott; Kuenzi, Amy; Bagamian, Karoun H.; Mills, James N.; Rollin, Pierre E.; Zanto, Susan N., and Douglass, Richard. Sampling frequency differentially influences interpretation of zoonotic pathogen and host dynamics: Sin Nombre virus and deer mice. Oecologia. 2011; 166:713-721.

Chevalier, Veronique; Rakotondrafara, Toky; Jourdan, Marion; Heraud, Jean Michel; Andriamanivo, Harena Rasamoelina; Durand, Benoit; Ravaomanana, julie; Rollin, Pierre E., and Rakotondravao, Rene. An Unexpected Recurrent Transmission of Rift Valley Fever Virus in Cattle in a Temperate and Mountainous Area of Madagascar. PLoS Neglected Tropical Diseases. 2011; 5(12):e1423.

Centers for Disease Control and Prevention. Congenital Lymphocytic Choriomeningitis - New York. Morbidity and Mortality Weekly Report. 2011; 60(1):16.

Damon IK. Status of human monkeypox clinical disease, epidemiology and research. Vaccine. 2011 Dec 18.

Dauphin, L.A., Walker, R.E., Petersen, J.M. and Bowen, M.D. 2011 Comparative evaluation of automated and manual commercial DNA extraction methods for detection of Francisella tularensis DNA from suspensions and spiked swabs using real-time PCR. Diag Micriobiol Infect Dis. 70(3):299-306.

Duncan, C., Kersh, G.J., Spraker, T., Patyk, K.A., Fitzpatrick, K.A., Massung, R.F., Gelatt, T. (2011) Coxiella burnetii in Northern Fur Seal (Callorhinus ursinus) placentas from St. Paul Island, Alaska. J. Vector Borne and Zoonotic Diseases. Oct 21. [Epub ahead of print] Engelthaler DM, TM Chiller, JA Schupp, J Colvin, SM Beckstrom-Sternberg, EM Driebe, T Moses, W Tembe, S Sinari, JS Beckstrom-Sternberg, A Christoforides, JV Pearson, J Carpten, P

Dodd, Kimberly A.; Bird, Brian H.; Khristova, Marina L.; Albarino, Cesar G.; Carroll, Serena A.; Comer, J. Andy; Erickson, Bobbie R.; Rollin, Pierre E., and Nichol, Stuart T. Ancient Ancestry of KFDV and AHFV Revealed by Complete Genome Analyses of Viruses Isolated from Ticks and Mammalian Hosts. PLoS Neglected Tropical Diseases. 2011; 5(10):e1352.

Folk, Scott; Steinbecker, Shari; Windmeyer, Joyce; MacNeil, Adam; Campbell, Shelley, and Rollin, Pierre E. Lymphocytic choriomeningitis with severe manifestations, Missouri, USA. Page 163 of 276

Emerging Infectious Diseases. 2011; 17(10):1973-1974.

Eremeeva, M.E. and G.A. Dasch. 2011. Rocky Mountain spotted fever (Rickettsia rickettsii). R, Katz and R. A. Zilinskas (Ed.) Encyclopedia of Bioterrorism Defense, 2nd Edition. J. Wiley and Sons: Hoboken, NJ.

Eremeeva, M.E. and G.A. Dasch. 2011. Epidemic Typhus (Rickettsia prowazekii). R, Katz and R. A. Zilinskas (Ed.) Encyclopedia of Bioterrorism Defense, 2nd Edition. J. Wiley and Sons: Hoboken, NJ.

Eremeeva, M.E. and G.A. Dasch. 2011. Chapter 52. Anaplasma, pp. 601-615. D. Liu (editor) Molecular detection of human bacterial pathogens. CRC Press.

Eremeeva, M.E. and G.A. Dasch. 2011. Chapter 58. Rickettsia. pp 683-700. D. Liu (editor) Molecular detection of human bacterial pathogens. CRC Press. Microbial Forensics, 2nd Edition, Elsevier.

Eremeeva M.E. and G.A. Dasch. 2011. Other rickettsioses. In: Principles and Practice of Pediatric Infectious Diseases (Long, Pickering, and Prober, eds.), 4th Edition. Elseiver, New York.

Eremeeva, M. E., and G. A. Dasch. 2011. The genus Rickettsia: microbiology, diversity and taxonomy. Revue Tunisienne d'Infectiologie Suppl. 5(2):7-11.

Eremeeva M.E., M.L. Zambrano, L. Anaya, L. Beati, S. Karpathy, M.M. Santos-SIlva, B. Salceda, D. Macbeth, H. Olguin, G.A. Dasch, and C. Alpuche Aranda. Rickettsia rickettsii in Rhipicephalus ticks, Mexicali, Mexico. 2011. J. Med. Entomol. 48(2): 418-421.

Estill CF, Baron PA, Beard JK, Hein MJ, Larsen LD, Deye GJ, Rose LJ, Hodges L. 2011. Comparison of air sampling methods for aerosolized spores of B. anthracis Sterne. J. Occ. Env. Hyg. 8: 179-186.

Fadeel, MA, Hoffmaster AR, Shi J, Pimentel G, Stoddard RA. Comparison of four commercial IgM and IgG ELISA kits for diagnosing brucellosis. Journal of Medical Microbiology. 2011: 60(12): 1767-1773.

Fagan RP, Neil KP, Sasich R, Lúquez C, Asaad H, Maslanka S, Khalil W. 2011. Initial recovery and rebound of type F intestinal colonization botulism after administration of investigational heptavalent botulinum antitoxin. Clin Infect Dis. 53:e125-e128.

Forsberg LS, Choudhury B, Leoff C, Marston CK, Hoffmaster AR, Saile E, Quinn CP, Kannenberg EL, Carlson RW. Secondary cell wall polysaccharides from Bacillus cereus strains G9241, 03BB87, and 03BB102 causing fatal pneumonia share similar glycosyl structures with the polysaccharides from Bacillus anthracis. Glycobiology. 2011: 21(7):934- Page 164 of 276

48.

Gee JE, Glass MB, Lackner G, Helsel LO, Daneshvar M, Hollis DG, Jordan J, Morey R, Steigerwalt A, Hertweck C. Characterization of Burkholderia rhizoxinica and B.endofungorum isolated from clinical specimens. PLOS One 2011; 6(1):e15731.

Gunther, Stephan; Feldmann, Heinz; Geisbert, Thomas W.; Hensley, Lisa E.; Rollin, Pierre E.; Nichol, Stuart T.; Stroher, Ute; Artsob, Harvey; Peters, Clarence J.; Ksiazek, Thomas G.; Becker, Stephan; Ter Meulen, Jan; Olschlager, Stephan; Schmidt-Chanasit, Jonas; Sudeck, Hinrich; Burchard, Gerd D., and Schmiedel, Stefan. Management of accidental exposure to ebola virus in the biosafety level 4 laboratory, Hamburg, Germany. Journal of Infectious Diseases. 2011; 204(Suppl 3):S785-S790.

Hantavirus pulmonary syndrome - Maine, April 2011. Morbidity and Mortality Weekly Report. 2011; 60(23):786.

Hornstra, H.M., Priestley, R.A., Georgia, S.M., Kachur, S., Birdsell, D.N., Hilsabeck, R., Gates, L.T., Samuel, J.E., Heinzen, R.A., Kersh, G.J., Keim, P., Massung, R.F., Pearson, P. (2011) Rapid Typing of Coxiella burnetii. Plos One. 6(11):e26201.

Hutson CL, Carroll DS, Gallardo-Romero N, Weiss S, Clemmons C, Hughes CM, Salzer JS, Olson VA, Abel J, Karem KL, Damon IK. Monkeypox disease transmission in an experimental setting: prairie dog animal model. PLoS One. 2011;6(12):e28295.

Kalb SR, Baudys J, Webb RP, Wright P, Smith TJ, Smith LA, Fernández R, Raphael BH, Maslanka SE, Pirkle JL, Barr JR. 2011. Discovery of a novel enzymatic cleavage site for botulinum neurotoxin F5. FEBS Lett [epub ahead of print]

Keckler MS, Carroll DS, Gallardo-Romero NF, Lash RR, Salzer JS, Weiss SL, Patel N, Clemmons CJ, Smith SK, Hutson CL, Karem KL, Damon IK. Establishment of the black- tailed prairie dog (Cynomys ludovicianus) as a novel animal model for comparing smallpox vaccines administered preexposure in both high- and low-dose monkeypox virus challenges. J Virol. 2011 Aug;85(15):7683-98.

Keim, A Peterson, D Terashita, and SA Balajee. Next-generation sequencing of Coccidioides immitis isolated during cluster investigation. Emerg Infect Dis 2011; 17: 227- 232 .

Kennedy JS, Gurwith M, Dekker CL, Frey SE, Edwards KM, Kenner J, Lock M, Empig C, Morikawa S, Saijo M, Yokote H, Karem K, Damon I, Perlroth M, Greenberg RN. Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults. J Infect Dis. 2011 Nov;204(9):1395-402.

Kersh, G.J., Oliver, L.D., Self, J.S., Fitzpatrick, K.A., Massung, R.F. (2011) Virulence of pathogenic Coxiella burnetii strains after growth in the absence of host cells. J. Vector Page 165 of 276

Borne and Zoonotic Diseases. 11(11):1433-1438.

Knust, Barbara; MacNeil, Adam; Wong, Susan J.; Backenson, P. Bryon; Gibbons, Aridth; Rollin, Pierre E., and Nichol, Stuart T. Exposure to lymphocytic choriomeningitis virus, New York, USA. Emerging Infectious Diseases. 2011; 17(7):1324-1325.

Kournikakis B, Martinez KF, McCleery RE, Shadomy SV, Ramos G. Anthrax Letters in an Open Office Environment: Effects of selected CDC response guidelines on personal exposure and building contamination. J Occup Environ Hyg. 2011: 8(2): 1-10.

Ksiazek, Thomas G.; Chua, Kaw Bing; Rota, Paul A., and Rollin, Pierre E. Hendra and Nipah viral infections. in: Guerrant, Richard L.; Walker, David H., and Weller, Peter F., eds. Tropical Infectious Diseases. Principles, Pathogens and Practice. 3nd ed. Philadelphia,PA: Elsevier ; 2011; pp. 352-354.

Ksiazek, Thomas G.; Rota, Paul A., and Rollin, Pierre E. A review of Nipah and Hendra viruses with an historical aside. Virus Research. 2011; 162:173-183.

Lembo T, Hampson K, Auty H, Beesley CA, Bessell P, Packer C, Halliday J, Fyumagwa R, Hoare R, Ernest E, Mentzel C, Mlengeya T, Stamey K, Wilkins PP, Cleaveland S. Serologic surveillance of anthrax in the Serengeti ecosystem, Tanzania, 1996-2009. Emerg Infect Dis. 2011: 17(3):387-94.

Liguori AP, Warrington SD, Ginther JL, Pearson T, Bowers J, Glass MB, Mayo M, Wuthiekanun V, Engelthaler D, Peacock SJ, Currie BJ, Wagner DM, Keim P, Tuanyok A. Diversity of 16S-23S rDNA Internal Transcribed Spacer (ITS) Reveals Phylogenetic Relationships in Burkholderia pseudomallei and Its Near-Neighbors. PLoS One. 2011:6 (12):e29323.

Logan NA, Hoffmaster AR, Shadomy SV, Stauffer KE. Bacillus and Other Aerobic Endospore-Forming Bacteria. In: Manual of Clinical Microbiology, 10th Edition. Versalovic J, Ed. in chief. ASM Press. 2011.

Luong, Lien T.; Vigliotti, Beth A.; Campbell, Shelley; Comer, James A.; Mills, James N., and Hudson, Peter J. Dynamics of Hantavirus Infection in Peromyscus leucopus of Central Pennsylvania. Vector Borne and Zoonotic Diseases. 2011; 11(11):1459-

Macneil, Adam; Farnon, Eileen C.; Morgan, Oliver W.; Gould, Philip; Boehmer, Tegan K.; Blaney, David D.; Wiersma, Petra; Tappero, Jordan W.; Nichol, Stuart T.; Ksiazek, Thomas G., and Rollin, Pierre E. Filovirus outbreak detection and surveillance: lessons from bundibugyo . Journal of Infectious Diseases. 2011; 204(Suppl 3):S761-S767.

MacNeil, Adam; Ksiazek, Thomas G., and Rollin, Pierre E. Hantavirus pulmonary syndrome, United States, 1993-2009. Emerging Infectious Diseases. 2011; 17(7):1195-1201. Page 166 of 276

Macneil, Adam; Nichol, Stuart T., and Spiropoulou, Christina F. Hantavirus pulmonary syndrome. Virus Research. 2011; 162:138-147.

MacNeil, Adam; Reed, Zachary, and Rollin, Pierre E. Serologic cross-reactivity of human IgM and IgG antibodies to five species of Ebola virus. PLoS Neglected Tropical Diseases. 2011; 5(6):e1175.

Macneil A, Abel J, Reynolds MG, Lash R, Fonnie R, Kanneh LD, Robert W, Lungay VK, Goba A, Moses LM, Damon IK, Karem K, Bausch DG. Serologic evidence of human orthopoxvirus infections in Sierra Leone. BMC Res Notes. 2011 Oct 28;4:465. 1464.

Mahdi, Mustafa; Erickson, Bobbie Rae; Comer, J. Andy; Nichol, Stuart T.; Rollin, Pierre E.; AlMazroa, Mohammed A., and Memish, Ziad A. Kyasanur Forest disease virus Alkhurma subtype in ticks, Najran Province, Saudi Arabia. Emerging Infectious Diseases. 2011; 17(5):945-947.

Marsh, Glenn A.; Haining, Jessica; Robinson, Rachel; Foord, Adam; Yamada, Manabu; Barr, Jennifer A.; Payne, Jean; White, John; Yu, Meng; Bingham, John; Rollin, Pierre E.; Nichol, Stuart T; Wang, Lin-Fa, and Middleton, Deborah. Ebola Reston virus infection of pigs: clinical significance and transmission potential. Journal of Infectious Diseases. 2011; 204 \(Suppl 3):S804-S809.

Maslanka SE, Luquez C, Raphael BH, Dykes J, and Joseph L. 2011. Utility of Botulinum Toxin ELISA A, B, E, F Kits for Clinical Laboratory Investigations of Human Botulism. The Botulinum Journal. 2: 72-92

Massung, R. F., G. A. Dasch, and M. E. Eremeeva. 2011. Rickettsia and Coxiella. In. Bruce Budowle, Steven E. Schutzer, Roger G. Breeze, Paul S. Keim and Stephen A. Morse (eds.)

Mattar, Salim; Guzman, Camilo; Arrazola, Justiniano; Soto, Ella; Barrios, Jose; Pini, Noemi; Levis, Silvana; Salazar-Bravo, Jorge, and Mills, James N. Antibody to arenaviruses in rodents, Caribbean Colombia. Emerging Infectious Diseases. 2011; 17(7):1315-1316.

Marston CK, Allen CA, Beaudry J, Price EP, Wolken SR, Pearson T, Keim P, Hoffmaster AR. Molecular Epidemiology of Anthrax Cases Associated with Recreational Use of Animal Hides and Yarn in the United States. PLoS One. 2011: 6(12): e28274.

Memish, Ziad A.; Albarrak, Ali; Almazroa, Mohammad A.; Al-Omar, Ibrahim; Alhakeem, Rafat; Assiri, Abdullah; Fagbo, Shamsudeen; MacNeil, Adam; Rollin, Pierre E.; Nageeb Abdullah, Nageeb, and Stephens, Gwen. Seroprevalence of Alkhurma and Other Hemorrhagic Fever Viruses, Saudi Arabia. Emerging Infectious Diseases. 2011; 17(12):2316-2318.

Mota BE, Gallardo-Romero N, Trindade G, Keckler MS, Karem K, Carroll D, Campos MA, Vieira LQ, da Fonseca FG, Ferreira PC, Bonjardim CA, Damon IK, Kroon EG. Adverse Page 167 of 276

events post smallpox-vaccination: insights from tail scarification infection in mice with Vaccinia virus. PLoS One. 2011 Apr 15;6(4):e18924. PubMed PMID: 21526210; PubMed Central PMCID: PMC3078145.

O'Connell HA, Rose LJ, Shams AM, Arduino MJ, Rice EW. 2011. Chlorine disinfection of Francisella tularensis. Let. Appl. Microbiolo. 52 84-6.

O'Sullivan BP, Torres B, Conidi G, Smole S, Gauthier C, Stauffer KE, Glass MB, Gee JE, Blaney D, Smith TL. Burkholderia pseudomallei infection in a child with cystic fibrosis: acquisition in the western hemisphere. Chest 2011:140(1):239-242.

Prabhu M., Nicholson W.L., Roche A.J., Kersh G.J., Fitzpatrick K.A., Oliver L.D., Massung R.F., Morrissey A.B., Bartlett J.A., Onyango J.J., Maro V.P., Kinabo G.D., Saganda W., Crump J.A. (2011) Q fever, spotted fever group and typhus group rickettsioses among hospitalized febrile patients in northern Tanzania. Clin Infect Dis. 53(4), e8-e15.

Rice AD, Gray SA, Li Y, Damon I, Moyer RW. An efficient method for generating poxvirus recombinants in the absence of selection. Viruses. 2011 Mar;3(3):217-32.

Reeves PM, Smith SK, Olson VA, Thorne SH, Bornmann W, Damon IK, Kalman D. Variola and monkeypox viruses utilize conserved mechanisms of virion motility and release that depend on abl and SRC family tyrosine kinases. J Virol. 2011 Jan;85(1):21-31.

Roess AA, Monroe BP, Kinzoni EA, Gallagher S, Ibata SR, Badinga N, Molouania TM, Mabola FS, Mombouli JV, Carroll DS, MacNeil A, Benzekri NA, Moses C, Damon IK, Reynolds MG. Assessing the effectiveness of a community intervention for monkeypox prevention in the Congo basin. PLoS Negl Trop Dis. 2011 Oct;5(10):e1356.

Rollin, Pierre E. Viral hemorrhagic fevers. in : Brunette, Gary W.; Kozarsky, Phyllis E.; Magill, Alan J.; Shlim, David R., and Whatley, Amanda D., eds. CDC Health Information for International Travel. The Yellow Book 2012. New York: Oxford University Press; 2011; pp. 329-332.

Rollin, Pierre E.; Nichol, Stuart T.; Zaki, Sherif, and Ksiazek, Thomas G. Arenaviruses and filoviruses. in: Versalovic, James; Carroll, Karen C.; Funke, Guido; Jorgensen, James H.; Landry, Marie Louise, and Warnock, David W., eds. Manual of Clinical Microbiology. 10th ed. Washington, DC: ASM Press; 2011; 2 pp. 1514-1529.

Rollin, Pierre E.; Rota, Paul; Zaki, Sherif, and Ksiazek, Thomas G. Hendra and Nipah viruses. in: Versalovic, James; Carroll, Karen C.; Funke, Guido; Jorgensen, James H.; Landry, Marie Louise, and Warnock, David W., eds. Manual of Clinical Microbiology. 10th ed. Washington, DC: ASM Press; 2011; 2 pp. 1479-1487.

Rose LJ, Hodges, L, O'Connell H, Noble-Wang J. 2011. National validation study of a cellulose sponge-wipe processing method for use after sampling Bacillus anthracis spores Page 168 of 276

from surfaces. Appl. Environ. Microbiol. 2011, 77(23):8355.

Shadomy SV, Heine HS, Boyer AE, Gallegos-Candela M, Lins RC, Barr JR, Pesik NT, Smith TL. Efficacy and Effect on Serum Lethal Factor Concentrations of Recommended and Alternative Antimicrobial Agents for Post-exposure Prophylaxis Following Bacillus anthracis Inhalation Exposure in a Murine Model. International Conference on Bacillus (Bacillus-ACT 2011). August, 2011, Bruges, Belgium.

Shams AM, O'Connell H, Arduino MJ, Rose LJ. 2011. Chlorine dioxide inactivation of bacterial threat agents. Let. Appl. Microbiol. 53:225-30.

Silva N., M.E. Eremeeva, T. Rozental, G. S. Ribeiro, C.D. Paddock, E. A. G. Ramos, A. R. Favacho, M.G. Reis, G.A. Dasch, E.R. de Lemos, and A. I. Ko. 2011. Eschar-associated spotted fever rickettsiosis, Bahia, Brazil. EID 17(2):275-278.

Smith SK, Self J, Weiss S, Carroll D, Braden Z, Regnery RL, Davidson W, Jordan R, Hruby DE, Damon IK. Effective antiviral treatment of systemic orthopoxvirus disease: ST-246 treatment of prairie dogs infected with monkeypox virus. J Virol. 2011 Sep;85(17):9176-87.

Thaipadunpanit J, Chierakul W, Wuthiekanun V, Limmathurotsakul D, Amornchai P, Boonslp S, Smythe SD, Limpaiboon R, Hoffmaster AR, Day NP, Peacock SJ. Diagnostic accuracy of real-time PCR assays targeting 16S rRNA and lipL32 genes for human Leptospirosis in Thailand: A case-control study. PLoS ONE. 2011: 6(1):e16236.

Wilder-Kofie TD, Lúquez C, Adler M, Dykes JK, Coleman J, Maslanka SE. 2011. An alternative in vivo method to refine the mouse bioassay for botulinum toxin detection. Comparative Medicine 61: 235-242.

Yadav, Pragya D.; Vincent, Martin J.; Khristova, Marina; Kale, Charuta; Nichol, Stuart T.; Mishra, Akhilesh C., and Mourya, Devendra T. Genomic analysis reveals Nairobi sheep disease virus to be highly diverse and present in both Africa, and in India in the form of the Ganjam virus variant. Infection Genetic and Evolution. 2011; 11(5):1111-1120.Belser JA, Zeng H, Katz JM, Tumpey TM. Infection with highly pathogenic H7 influenza viruses results in an attenuated proinflammatory cytokine and chemokine response early after infection. The Journal of Infectious Diseases. 2011;203:40-8.

Belser JA, Zeng H, Katz JM, Tumpey TM. Ocular tropism of influenza A viruses: Identification of H7 subtype-specific host responses in human respiratory and ocular cells. Journal of Virology. 2011;85(19):10117-25.

Gambaryan AS, Lomakina NF, Boravleva EY, Kropotkina EA, Mashin VV, Krasilnikov IV, Klimov AI, Rudenko LG. Comparative safety, immunogenicity, and efficacy of several anti- H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine). Influenza and Other Respiratory Viruses. 2011;doi:10.1111/j.1750- Page 169 of 276

2659-2011.00291.x.

Gustin KM, Maines TR, Belser JA van Hoeven N, Lu X, Dong L, Isakova-Sivak I, Chen L- M, Voeten J, Heldens J, van den Bosch H, Cox NJ, Tumpey TM, Klimov AI, Rudenko L, Donis RO, Katz JM. Comparative immunogenicity and cross-clade protective efficacy of mammalian cell-grown inactivated and live attenuated H5N1 reassortant vaccines in ferrets. The Journal of Infectious Diseases. 2011;204:1491-9.

Karpala AJ, Bingham J, Schat KA, Chen L-M, Donis RO, Lowenthal JW, Bean AG. Highly pathogenic (H5N1) avian influenza induces an inflammatory T helper type 1 cytokine response in the chicken. Journal oa Interferon & Cytokine Research. 2011;31(4):393-

Li Y, Li J, Belisle S, Baskin CR, Tumpey TM, Katze MG. Differential microRNA expression and virulence of avian, 1918 reassortant, and reconstructed 1918 influenza A viruses. Virology. 2011;421:105-113.

Maines TR, Chen L-M, Belser JA, Van Hoeven N, Smith E, Donis RO, Tumpey TM, Katz JM. Multiple genes contribute to the virulent phenotype observed in ferrets of an H5N1 influenza virus isolated from Thailand in 2004. Virology. 2011;413(2):226-30.

Maines TR, Chen L-M, Van Hoeven N, Tumpey TM, Blixt O, Belser JA, Gustin KM, Pearce MB, Pappas C, Stevens J, Cox NJ, Paulson JC, Raman R, Sasisekharan R, Katz JM, Donis RO. Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. Virology. 2011;413:139-47.

Shinde V, Hanshaoworakul W, Simmerman JM, Narueponjirakul U, Sanasuttipun W, Kaewchana S, Areechokechai D, Ungchusak K, Fry AM. A comparison of clinical and epidemiological characteristics of fatal human infections with H5N1 and human influenza viruses in Thailand, 2004-2006. 2011;6(4):e14809.

Spesock A, Malur M, Hossain MJ, Chen L-M, Njaa BL, Davis CT, Lipatov AS, York IA, Krug RM, Donis RO. The virulence of 1997 H5N1 influenza viruses in the mouse model is increased by correcting a defect in their NS1 proteins. Journal of Virology. 2011;85(14):7048-58.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Activities include developing diagnostic assays for public health, conducting molecular and antigentic characterization of organisms, determing pathogenictiy and virulence of infectious agents, determining the natural history of infectious organisms, and conducting epidemiologic studies and surveillance for diseases.

Page 170 of 276

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins

(iii) Outdoor Studies: None

Page 171 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

CDC, OID, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector Borne Diseases (DVBD) - Ft. Collins

2. Where is it located (provide both address and geographical location)?

Centers for Disease Control and Prevention, U.S. Department of Health and Human Services 3150 Rampart Road

Fort Collins, Colorado 80521

3. Floor area of laboratory areas by containment level:

BL2 66 (sqM) BL3 1142 (sqM) BL4 0 (sqM) Total laboratory floor area 1208 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 67

(ii) Division of personnel:

Military 0

Civilian 67

(iii) Division of personnel by category:

Scientists 54

Engineers 0

Technicians 10

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology Ecology Epidemiology Medicine Page 172 of 276

Microbiology Molecular Biology Public Health Statistics Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 10

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

Centers for Disease Control and Prevention (CDC) U.S. Department of Homeland Security (DHS) U.S. Department of Defense (DOD) - partly

(vii) What are the funding levels for the following program areas: Research $ 1,220,244 Development $ 610,121 Test and evaluation $ 610,121 Total $ 2,440,486

(viii)Briefly describe the publication policy of the facility: Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Agency.

The clearance policy for information products disseminated outside CDC for public use, is available online at: http://www.cdc.gov/od/science/policies

CDC Policy on "Oversight and clearance of dual use research of concern," is available online at:http://aops-mas-iis.cdc.gov/Policy/Doc/policy516.pdf

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Book Chapter: Arboviruses. Robert S. Lanciotti and Theodore F. Tsai. Manual of Clinical Microbiology - 10th edition. Chapter 93 2011. Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach J, Marfin AA, Solomon T, Tsai TF, Tsu V, Ginsberg A. Estimated global frequency and incidence of Page 173 of 276

Japanese encephalitis. Bull WHO 2011 (Aug). Available online at http://www.who.int/bulletin/online_first/10-085233.pdf CDC. Japanese Encephalitis in Two Children - United States, 2010. MMWR 2011 (Mar);60(9):276-78. CDC. Recommendations for Use of a Booster Dose of Inactivated Vero Cell Culture- Derived Japanese Encephalitis Vaccine - Advisory Committee on Immunization Practices, 2011. MMWR 2011 (May);60(20):661-63. CDC. Update on Japanese Encephalitis Vaccine for Children - United States, May 2011. MMWR 2011 (May);60(20):664-65. Hills S, Fischer M, Solomon T. Japanese encephalitis: Epidemiology, diagnosis, treatment and prevention. In Basow DS (Ed) UpToDate. Waltham, MA. 2009. (Updated 2011). Hills S, Nett R, Fischer M. Japanese encephalitis. In: Health Information for International Travel, 2012. Eds: G Brunette. Atlanta: U.S. Department of Health and Human Services, Public Health Service, 2011 (Jun):205-14. Lambert AJ, Blair CD, D'Anton M, Ewing W, Harborth M, Seiferth R, Xiang J, Lanciotti RS. Japanese encephalitis in two children------United States, 2010. 2011. MMWR 16, 276- 278. Paul RC, Rahman M, Gurley ES, Hossain MJ, Diorditsa S, Hasan ASMM, Banu SS, Alamgir ASM, Rahman, MA, Sandhu H, Fischer M, Luby SP. A novel low cost approach to estimate the incidence of Japanese encephalitis in the catchment area of three hospitals in Bangladesh. Am J Trop Med Hyg 2011 (Aug); 85(2):379-385. Powers, A.M. and Roehrig, J.T. 2011. Alphaviruses. In: Diagnostic Virology Protocols, second edition; Methods in Molecular Biology, vol. 665. pp 17-38. Powers, Ann M. and Jeremy P. Ledermann. 2011. Venezuelan Equine Encephalitis Virus. In: Molecular Detection Of Human Viral Pathogens. Chapter 33, Pp 373-382. Zhang S, Yin Z, Suraratdecha C, Liu X, Li Y, Hills S, et al. Knowledge, attitudes and practices of caregivers regarding Japanese encephalitis in Shaanxi Province, China. Public Health 2011; 125:79-83. Schotthoefer AM, Bearden SW, Holmes JL, Vetter SM, Montenieri JA, Williams SK, Graham CB, Woods ME, Eisen RJ, Gage KL. Effects of temperature on the transmission of Yersinia pestis by the flea, Xenopsylla cheopis, in the late phase period. Parasit Vectors 2011 29:4:411, 2011 Ben Ari T, Neerinckx S, Gage K, Kreppel K, Laudisoit A, Leirs H, Stenseth NC. Plague and climate: Scales matter. PLoS Pathogens 7(9): e1002160. doi:10.1371/journal.ppat.1002160, 2011. Brown HE, Levy C, Enscore RE, Schriefer M, DiLiberto T, Gage KL, Eisen RE. Annual seroprevalence of Yersinia pestis in coyotes as predictors of interannual variation in reports of human plague cases in Arizona, USA. Vector-Borne Zoonotic Diseases (Epub - July 14), 2011. Eisen RJ, Gage KL. Transmission of flea-borne zoonotic agents. Annual Review of Entomology 57:61-82, 2011. Gage KL. Plague and Yersinia Infections. In: Goldman's Cecil Medicine, 24th Edition. Ed. Goldman L, Schafer AI. Saunders Elsevier, Philadelphia. Chapter 320, pp. 1895-1900, 2011. Prabhu M., Nicholson W.L., Roche A.J., Kersh G.J., Fitzpatrick K.A., Oliver L.D., Massung R.F., Morrissey A.B., Bartlett J.A., Onyango J.J., Maro V.P., Kinabo G.D., Saganda W., Page 174 of 276

Crump J.A. (2011) Q fever, spotted fever group and typhus group rickettsioses among hospitalized febrile patients in northern Tanzania. Clin Infect Dis. 53(4), e8-e15. Kersh, G.J., Oliver, L.D., Self, J.S., Fitzpatrick, K.A., Massung, R.F. (2011) Virulence of pathogenic Coxiella burnetii strains after growth in the absence of host cells. J. Vector Borne and Zoonotic Diseases. Aug 25 (Epub) Duncan, C., Kersh, G.J., Spraker, T., Patyk, K.A., Fitzpatrick, K.A., Massung, R.F., Gelatt, T. (2011) Coxiella burnetii in Northern Fur Seal (Callorhinus ursinus) placentas from St. Paul Island, Alaska. J. Vector Borne and Zoonotic Diseases. Oct 21 (Epub) Kersh, G.J., Lambourn, D.M., Raverty, S.A., Fitzpatrick, K.A., Joshua S. Self, J.S., Akmajian, A.M., Jeffries, S.J., Huggins, J., Drew, C.P., Zaki, S.R., and Massung, R.F. (2011) Coxiella burnetii infection of Marine Mammals in the Pacific Northwest, 1997-2010. J. Wildlife Diseases. in press Hornstra, H.M., Priestley, R.A., Georgia, S.M., Kachur, S., Birdsell, D.N., Hilsabeck, R., Gates, L.T., Samuel, J.E., Heinzen, R.A., Kersh, G.J., Keim, P., Massung, R.F., Pearson, P. (2011) Rapid Typing of Coxiella burnetii. Plos One. in press Brown HE, Yates KF, Dietrich G, MacMillan K, Graham CB, Reese SM, Helterbrand WS, Nicholson WL, Blount K, Mead PS, Patrick SL, Eisen RJ. An acarologic survey and Amblyomma americanum distribution map with implications for tularemia risk in Missouri. Am J Trop Med Hyg. 2011; 84(3):411-419. Bjork A, Anderson A. Notes from the field: Q fever outbreak associated with goat farms, Washington and Montana, 2011. MMWR 2011; 60:1393.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: DVBD possesses many of the select agents that are on the Department of Health and Human Services (HHS) and HHS/US Department of Agriculture overlap lists. Within CDC, DVBD has the primary responsibility for research on tularemia, plague and the alphaviruses. This research involves development of assays for surveillance and detection of each agent and molecular and antigenic characterization.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins

Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category B Priority Pathogens

• Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 175 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Integrated Research Facility (IRF) - Rocky Mountain Laboratories (RML)

2. Where is it located (provide both address and geographical location)?

903 South 4th St. Hamilton, Montana 59840

3. Floor area of laboratory areas by containment level:

BL2 1361 (sqM) BL3 56 (sqM) BL4 631 (sqM) Total laboratory floor area 2048 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 96

(ii) Division of personnel:

Military 0

Civilian 96

(iii) Division of personnel by category:

Scientists 70

Engineers 0

Technicians 23

Administrative and support staff 3

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology Biology Chemistry Immunology Medicine Microbiology Page 176 of 276

Molecular Biology Parasitology Pathogenesis Prionology Rickettsiology Vaccine Evaluation Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 2

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas: Research $ 24,946,139 Development $ 0 Test and evaluation $ 0 Total $ 24,946,139

(viii) Briefly describe the publication policy of the facility: All researchers are encouraged to publish results in peer-reviewed open literature.

The NIH Public Access Policy (http://publicaccess.nih.gov/policy.htm ) ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the National Library of Medicine's digital archive PubMed Central upon acceptance for publication. To help advance science and improve human health, the Policy requires that these papers are accessible to the public on PubMed Central no later than 12 months after publication.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Aleksandrowicz P, Marzi A, Biedenkopf N, Beimforde N, Becker S, Hoenen T, Feldmann H, Schnittler HJ. Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J Infect Dis. 2011 Nov;204 Suppl 3:S957-67. PubMed PMID: 21987776; Page 177 of 276

PubMed Central PMCID: PMC3189988.

Baron GS, Hughson AG, Raymond GJ, Offerdahl DK, Barton KA, Raymond LD, Dorward DW, Caughey B. Effect of glycans and the glycophosphatidylinositol anchor on strain dependent conformations of scrapie prion protein: improved purifications and infrared spectra. Biochemistry. 2011 May 31;50(21):4479-90. Epub 2011 May 3. PubMed PMID: 21539311; PubMed Central PMCID: PMC3101284.

Barton KA, Caughey B. Is PrP the road to ruin? EMBO J. 2011 May 18;30(10):1882-4. Review. PubMed PMID: 21593729; PubMed Central PMCID: PMC3098489.

Bauler TJ, Chase JC, Bosio CM. IFN-Î² mediates suppression of IL-12p40 in human dendritic cells following infection with virulent Francisella tularensis. J Immunol. 2011 Aug 15;187(4):1845-55. Epub 2011 Jul 13. PubMed PMID: 21753150; PubMed Central PMCID: PMC3150225.

Beare PA, Gilk SD, Larson CL, Hill J, Stead CM, Omsland A, Cockrell DC, Howe D, Voth DE, Heinzen RA. Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in human macrophages. MBio. 2011 Sep 1;2(4):e00175-11.doi: 10.1128/mBio.00175-11. Print 2011. PubMed PMID: 21862628; PubMed Central PMCID: PMC3163939.

Beare PA, Sandoz KM, Omsland A, Rockey DD, Heinzen RA. Advances in genetic manipulation of obligate intracellular bacterial pathogens. Front Microbiol. 2011;2:97. Epub 2011 May 2. PubMed PMID: 21833334; PubMed Central PMCID: PMC3153054.

Bosio CM. The subversion of the immune system by francisella tularensis. Front Microbiol. 2011;2:9. Epub 2011 Feb 1. PubMed PMID: 21687406; PubMed Central PMCID: PMC3109352.

Bossart KN, Geisbert TW, Feldmann H, Zhu Z, Feldmann F, Geisbert JB, Yan L, Feng YR, Brining D, Scott D, Wang Y, Dimitrov AS, Callison J, Chan YP, Hickey AC, Dimitrov DS, Broder CC, Rockx B. A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge. Sci Transl Med. 2011 Oct 19;3(105):105ra103. PubMed PMID: 22013123.

Bourret TJ, Boylan JA, Lawrence KA, Gherardini FC. Nitrosative damage to free and zinc- bound cysteine thiols underlies nitric oxide toxicity in wild-type Borrelia burgdorferi. Mol Microbiol. 2011 Jul;81(1):259-73. doi:10.1111/j.1365-2958.2011.07691.x. Epub 2011 May 19. PubMed PMID: 21564333; PubMed Central PMCID: PMC3147059.

Brining DL, Mattoon JS, Kercher L, LaCasse RA, Safronetz D, Feldmann H, Parnell MJ. Thoracic radiography as a refinement methodology for the study of H1N1 influenza in cynomologus macaques (Macaca fascicularis). Comp Med. 2010 Oct;60(5):389-95. PubMed Page 178 of 276

PMID: 21262125; PubMed Central PMCID: PMC2958208.

Brown KS, Safronetz D, Marzi A, Ebihara H, Feldmann H. Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus. J Virol. 2011 Dec;85(23):12781-91. Epub 2011 Sep 14. PubMed PMID: 21917979; PubMed Central PMCID: PMC3209372.

Cilloniz C, Ebihara H, Ni C, Neumann G, Korth MJ, Kelly SM, Kawaoka Y,Feldmann H, Katze MG. Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection. J Virol. 2011 Sep;85(17):9060-8. Epub 2011 Jul 6. PubMed PMID: 21734050; PubMed Central PMCID: PMC3165855.

Clark TR, Ellison DW, Kleba B, Hackstadt T. Complementation of Rickettsia rickettsii RelA/SpoT restores a nonlytic plaque phenotype. Infect Immun. 2011 Apr;79(4):1631-7. Epub 2011 Feb 7. PubMed PMID: 21300770; PubMed Central PMCID: PMC3067566.

Clark TR, Lackey AM, Kleba B, Driskell LO, Lutter EI, Martens C, Wood DO, Hackstadt T. Transformation frequency of a mariner-based transposon in Rickettsia rickettsii. J Bacteriol. 2011 Sep;193(18):4993-5. Epub 2011 Jul 15. PubMed PMID: 21764933; PubMed Central PMCID: PMC3165637.

Conlan JW, Chen W, Bosio CM, Cowley SC, Elkins KL. Infection of mice with Francisella as an immunological model. Curr Protoc Immunol. 2011 Apr; Chapter 19:Unit 19.14. PubMed PMID: 21462168.

Cooper KG, Winfree S, Malik-Kale P, Jolly C, Ireland R, Knodler LA, Steele-Mortimer O. Activation of Akt by the bacterial inositol phosphatase, SopB, is wortmannin insensitive. PLoS One. 2011;6(7):e22260. Epub 2011 Jul 14. PubMed PMID: 21779406; PubMed Central PMCID: PMC3136525.

DeLeo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN. Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18091-6. Epub 2011 Oct 24. PubMed PMID: 22025717; PubMed Central PMCID: PMC3207694. de Wit E, Bushmaker T, Scott D, Feldmann H, Munster VJ. Nipah virus transmission in a hamster model. PLoS Negl Trop Dis. 2011 Dec;5(12):e1432. Epub 2011 Dec 13. PubMed PMID: 22180802; PubMed Central PMCID: PMC3236726. de Wit E, Munster VJ, Metwally SA, Feldmann H. Assessment of rodents as animal models for Reston ebolavirus. J Infect Dis. 2011 Nov;204 Suppl 3:S968-72. PubMed PMID: Page 179 of 276

21987777; PubMed Central PMCID: PMC3189989.

Ebihara H, Rockx B, Marzi A, Feldmann F, Haddock E, Brining D, LaCasse RA, Gardner D, Feldmann H. Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. J Infect Dis. 2011 Nov;204 Suppl 3:S991-9. PubMed PMID: 21987781; PubMed Central PMCID: PMC3189992.

Engel AR, Mitzel DN, Hanson CT, Wolfinbarger JB, Bloom ME, Pletnev AG. Chimeric tick-borne encephalitis/dengue virus is attenuated in Ixodes scapularis ticks and Aedes aegypti mosquitoes. Vector Borne Zoonotic Dis. 2011 Jun;11(6):665-74. Epub 2010 Dec 13. PubMed PMID: 21142950; PubMed Central PMCID: PMC3115420.

Falzarano D, Feldmann F, Grolla A, Leung A, Ebihara H, Strong JE, Marzi A, Takada A, Jones S, Gren J, Geisbert J, Jones SM, Geisbert TW, Feldmann H. Single immunization with a monovalent vesicular stomatitis virus-based vaccine protects nonhuman primates against heterologous challenge with Bundibugyo ebolavirus. JInfect Dis. 2011 Nov;204 Suppl 3:S1082-9. PubMed PMID: 21987745; PubMed Central PMCID: PMC3189995.

Falzarano D, Geisbert TW, Feldmann H. Progress in filovirus vaccine development: evaluating the potential for clinical use. Expert Rev Vaccines. 2011 Jan;10(1):63-77. Review. PubMed PMID: 21162622.

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849- 62. Review. PubMed PMID: 21084112.

Fields KA, Heinzen RA, Carabeo R. The obligate intracellular lifestyle. Front Microbiol. 2011;2:99. Epub 2011 May 5. PubMed PMID: 21747803; PubMed Central PMCID: PMC3129005.

Geier H, Celli J. Phagocytic receptors dictate phagosomal escape and intracellular proliferation of Francisella tularensis. Infect Immun. 2011 Jun;79(6):2204-14. Epub 2011 Mar 21. PubMed PMID: 21422184; PubMed Central PMCID: PMC3125850.

Geisbert TW, Feldmann H. Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections. J Infect Dis. 2011 Nov;204Suppl 3:S1075-81. Review. PubMed PMID: 21987744; PubMed Central PMCID: PMC3218670.

Hinnebusch BJ, Jarrett CO, Callison JA, Gardner D, Buchanan SK, Plano GV. Role of the Yersinia pestis Ail protein in preventing a protective polymorphonuclear leukocyte response during bubonic plague. Infect Immun. 2011 Dec;79(12):4984-9. Epub 2011 Oct 3. PubMed PMID: 21969002; PubMed Central PMCID: PMC3232667.

Hornstra HM, Priestley RA, Georgia SM, Kachur S, Birdsell DN, Hilsabeck R, Gates LT, Samuel JE, Heinzen RA, Kersh GJ, Keim P, Massung RF, Pearson T. Rapid typing of Coxiella burnetii. PLoS One. 2011;6(11):e26201. Epub 2011 Nov 2. PubMed PMID: Page 180 of 276

22073151; PubMed Central PMCID: PMC3206805.

Klingeborn M, Race B, Meade-White KD, Chesebro B. Lower specific infectivity of protease-resistant prion protein generated in cell-free reactions. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):E1244-53. Epub 2011 Nov 7. PubMed PMID: 22065744; PubMed Central PMCID: PMC3228482.

Klingeborn M, Race B, Meade-White KD, Rosenke R, Striebel JF, Chesebro B. Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol. 2011 Feb;85(4):1484-94. Epub 2010 Dec 1. PubMed PMID: 21123371; PubMed Central PMCID: PMC3028874.

Knodler LA, Celli J. Eating the strangers within: host control of intracellular bacteria via xenophagy. Cell Microbiol. 2011 Sep;13(9):1319-27. doi: 10.1111/j.1462- 5822.2011.01632.x. Epub 2011 Jul 10. Review. PubMed PMID: 21740500; PubMed Central PMCID: PMC3158265.

Knodler LA, Ibarra JA, Pérez-Rueda E, Yip CK, Steele-Mortimer O. Coiled-coil domains enhance the membrane association of Salmonella type III effectors. Cell Microbiol. 2011 Oct;13(10):1497-517. doi: 10.1111/j.1462-5822.2011.01635.x. Epub 2011 Jul 11. PubMed PMID: 21679290.

Kobayashi SD, DeLeo FR. A MRSA-terious enemy among us: boosting MRSA vaccines. Nat Med. 2011 Feb;17(2):168-9. PubMed PMID: 21297611.

Kobayashi SD, Malachowa N, Whitney AR, Braughton KR, Gardner DJ, Long D, Bubeck Wardenburg J, Schneewind O, Otto M, Deleo FR. Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J Infect Dis. 2011 Sep 15;204(6):937-41. PubMed PMID: 21849291; PubMed Central PMCID: PMC3156927.

Kühl A, Banning C, Marzi A, Votteler J, Steffen I, Bertram S, Glowacka I, Konrad A, Stürzl M, Guo JT, Schubert U, Feldmann H, Behrens G, Schindler M, Pöhlmann S. The Ebola virus glycoprotein and HIV-1 Vpu employ different strategies to counteract the antiviral factor tetherin. J Infect Dis. 2011 Nov;204 Suppl 3:S850-60. PubMed PMID: 21987761; PubMed Central PMCID: PMC3189996.

Kühl A, Hoffmann M, Müller MA, Munster VJ, Gnirss K, Kiene M, Tsegaye TS, Behrens G, Herrler G, Feldmann H, Drosten C, Pöhlmann S. Comparative analysis of Ebola virus glycoprotein interactions with human and bat cells. J Infect Dis.2011 Nov;204 Suppl 3:S840-9. PubMed PMID: 21987760; PubMed Central PMCID: PMC3189982.

Lockwood S, Voth DE, Brayton KA, Beare PA, Brown WC, Heinzen RA, Broschat SL. Identification of Anaplasma marginale type IV secretion system effector proteins. PLoS One. 2011;6(11):e27724. Epub 2011 Nov 28. PubMed PMID: 22140462; PubMed Central Page 181 of 276

PMCID: PMC3225360.

Malachowa N, DeLeo FR. Staphylococcus aureus survival in human blood. Virulence. 2011 Nov-Dec;2(6):567-9. Epub 2011 Nov 1. PubMed PMID: 21971187;PubMed Central PMCID: PMC3260549.

Malachowa N, Whitney AR, Kobayashi SD, Sturdevant DE, Kennedy AD, Braughton KR, Shabb DW, Diep BA, Chambers HF, Otto M, DeLeo FR. Global changes in Staphylococcus aureus gene expression in human blood. PLoS One. 2011 Apr 15;6(4):e18617. PubMed PMID: 21525981; PubMed Central PMCID: PMC3078114.

Malik-Kale P, Jolly CE, Lathrop S, Winfree S, Luterbach C, Steele-Mortimer O. Salmonella - at home in the host cell. Front Microbiol. 2011;2:125. Epub 2011 Jun 3. PubMed PMID: 21687432; PubMed Central PMCID: PMC3109617.

Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H. Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy. J Infect Dis. 2011 Nov;204 Suppl 3:S1066-74. PubMed PMID: 21987743; PubMed Central PMCID: PMC3203393.

Mehedi M, Falzarano D, Seebach J, Hu X, Carpenter MS, Schnittler HJ, Feldmann H. A new Ebola virus nonstructural glycoprotein expressed through RNA editing. J Virol. 2011 Jun;85(11):5406-14. Epub 2011 Mar 16. PubMed PMID: 21411529; PubMed Central PMCID: PMC3094950.

Mital J, Hackstadt T. Diverse requirements for SRC-family tyrosine kinases distinguish chlamydial species. MBio. 2011 Mar 22;2(2). pii: e00031-11. doi:10.1128/mBio.00031-11. Print 2011. PubMed PMID: 21427287; PubMed Central PMCID: PMC3063380.

Mital J, Hackstadt T. Role for the SRC family kinase Fyn in sphingolipid acquisition by chlamydiae. Infect Immun. 2011 Nov;79(11):4559-68. Epub 2011 Sep 6. PubMed PMID: 21896774; PubMed Central PMCID: PMC3257913.

Moore ER, Mead DJ, Dooley CA, Sager J, Hackstadt T. The trans-Golgi SNARE syntaxin 6 is recruited to the chlamydial inclusion membrane. Microbiology. 2011 Mar;157(Pt 3):830- 8. Epub 2010 Nov 25. PubMed PMID: 21109560; PubMed Central PMCID: PMC3081085.

Moore RA, Timmes AG, Wilmarth PA, Safronetz D, Priola SA. Identification and removal of proteins that co-purify with infectious prion protein improves the analysis of its secondary structure. Proteomics. 2011 Oct;11(19):3853-65. doi:10.1002/pmic.201100253. Epub 2011 Sep 7. PubMed PMID: 21805638.

Nakayama E, Tomabechi D, Matsuno K, Kishida N, Yoshida R, Feldmann H, Takada A. Antibody-dependent enhancement of Marburg virus infection. J Infect Dis. 2011 Nov;204 Page 182 of 276

Suppl 3:S978-85. PubMed PMID: 21987779; PubMed Central PMCID: PMC3189991.

Ogawa H, Miyamoto H, Ebihara H, Ito K, Morikawa S, Feldmann H, Takada A. Detection of all known filovirus species by reverse transcription-polymerase chain reaction using a primer set specific for the viral nucleoprotein gene. J Virol Methods. 2011 Jan;171(1):310-3. Epub 2010 Nov 17. PubMed PMID: 21093485.

Omsland A, Beare PA, Hill J, Cockrell DC, Howe D, Hansen B, Samuel JE, Heinzen RA. Isolation from animal tissue and genetic transformation of Coxiella burnetii are facilitated by an improved axenic growth medium. Appl Environ Microbiol. 2011 Jun;77(11):3720-5. Epub 2011 Apr 8. PubMed PMID: 21478315; PubMed Central PMCID: PMC3127619.

Omsland A, Heinzen RA. Life on the outside: the rescue of Coxiella burnetii from its host cell. Annu Rev Microbiol. 2011;65:111-28. Review. PubMed PMID:21639786.

Orrú CD, Caughey B. Prion seeded conversion and amplification assays. Top Curr Chem. 2011;305:121-33. Review. PubMed PMID: 21678135.

Orrú CD, Wilham JM, Raymond LD, Kuhn F, Schroeder B, Raeber AJ, Caughey B. Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. MBio. 2011 May 10;2(3):e00078-11. doi: 10.1128/mBio.00078-11. Print 2011. PubMed PMID: 21558432; PubMed Central PMCID: PMC3101782.

Pathmajeyan MS, Patel SA, Carroll JA, Seib T, Striebel JF, Bridges RJ, Chesebro B. Increased excitatory amino acid transport into murine prion protein knockout astrocytes cultured in vitro. Glia. 2011 Nov;59(11):1684-94. doi:10.1002/glia.21215. Epub 2011 Jul 15. PubMed PMID: 21766339.

Race B, Meade-White K, Miller MW, Fox KA, Chesebro B. In vivo comparison of chronic wasting disease infectivity from deer with variation at prion protein residue 96. J Virol. 2011 Sep;85(17):9235-8. Epub 2011 Jun 22. PubMed PMID: 21697479; PubMed Central PMCID: PMC3165848.

Rigby KM, Deleo FR. Neutrophils in innate host defense against Staphylococcus aureus infections. Semin Immunopathol. 2012 Mar;34(2):237-59. Epub 2011 Nov 12.PubMed PMID: 22080185.

Rockx B, Brining D, Kramer J, Callison J, Ebihara H, Mansfield K, Feldmann H.Clinical outcome of henipavirus infection in hamsters is determined by the route and dose of infection. J Virol. 2011 Aug;85(15):7658-71. Epub 2011 May 18. PubMed PMID: 21593160; PubMed Central PMCID: PMC3147900.

Rockx B, Feldmann F, Brining D, Gardner D, LaCasse R, Kercher L, Long D, Rosenke R, Virtaneva K, Sturdevant DE, Porcella SF, Mattoon J, Parnell M, Baric RS, Feldmann H. Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus Page 183 of 276

macaques. PLoS One. 2011 Apr 20;6(4):e18558. PubMed PMID: 21533129; PubMed Central PMCID: PMC3080360.

Safronetz D, Haddock E, Feldmann F, Ebihara H, Feldmann H. In vitro and in vivo activity of ribavirin against Andes virus infection. PLoS One. 2011;6(8):e23560. Epub 2011 Aug 10. PubMed PMID: 21853152; PubMed Central PMCID: PMC3154477.

Safronetz D, Zivcec M, Lacasse R, Feldmann F, Rosenke R, Long D, Haddock E, Brining D, Gardner D, Feldmann H, Ebihara H. Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus. PLoS Pathog.2011 Dec;7(12):e1002426. Epub 2011 Dec 15. PubMed PMID: 22194683; PubMed Central PMCID: PMC3240607.

Smirnovas V, Baron GS, Offerdahl DK, Raymond GJ, Caughey B, Surewicz WK. Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange. Nat Struct Mol Biol. 2011 Apr;18(4):504-6. Epub 2011 Mar 27. PubMed PMID: 21441913.

Spiegelberg L, Wahl-Jensen V, Kolesnikova L, Feldmann H, Becker S, Hoenen T. Genus- specific recruitment of filovirus ribonucleoprotein complexes into budding particles. J Gen Virol. 2011 Dec;92(Pt 12):2900-5. Epub 2011 Sep 7. PubMed PMID: 21900424.

Striebel JF, Race B, Meade-White KD, LaCasse R, Chesebro B. Strain specific resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171. PLoS Pathog. 2011 Sep;7(9):e1002275. Epub 2011 Sep 29. PubMed PMID: 21980292; PubMed Central PMCID: PMC3182929.

Sun YC, Koumoutsi A, Jarrett C, Lawrence K, Gherardini FC, Darby C, Hinnebusch BJ. Differential control of Yersinia pestis biofilm formation in vitro and in the flea vector by two c-di-GMP diguanylate cyclases. PLoS One. 2011 Apr 29;6(4):e19267. PubMed PMID: 21559445; PubMed Central PMCID: PMC3084805.

Taylor RT, Best SM. Assessing ubiquitination of viral proteins: Lessons from flavivirus NS5. Methods. 2011 Oct;55(2):166-71. Epub 2011 Aug 10. PubMed PMID: 21855635; PubMed Central PMCID: PMC3208789.

Taylor RT, Lubick KJ, Robertson SJ, Broughton JP, Bloom ME, Bresnahan WA, Best SM. TRIM79Î±, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase. Cell Host Microbe. 2011 Sep 15;10(3):185-96. doi: 10.1016/j.chom.2011.08.004. PubMed PMID: 21925107; PubMed Central PMCID: PMC3182769.

Tribouillard-Tanvier D, Carroll JA, Moore RA, Striebel JF, Chesebro B. Role of Cyclophilin A from Brains of Prion-InfectedMice in Stimulation of Cytokine Release by Microglia and Astroglia In Vitro. J Biol Chem. 2011 Dec 16. [Epub ahead of print] PubMed Page 184 of 276

PMID: 22179611.

Tsuda Y, Caposio P, Parkins CJ, Botto S, Messaoudi I, Cicin-Sain L, Feldmann H, Jarvis MA. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. PLoS Negl Trop Dis. 2011 Aug;5(8):e1275. Epub 2011 Aug 9. PubMed PMID: 21858240; PubMed Central PMCID: PMC3153429.

Tsuda Y, Safronetz D, Brown K, LaCasse R, Marzi A, Ebihara H, Feldmann H. Protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the Syrian hamster model of lethal Ebola virus infection. J Infect Dis. 2011 Nov;204 Suppl 3:S1090-7. PubMed PMID: 21987746; PubMed Central PMCID: PMC3189997.

Twardoski B, Feldmann H, Bloom ME, Ward J. Modern dosimetric tools for (60) Coirradiation at high containment laboratories. Int J Radiat Biol. 2011 Oct;87(10):1039-44. PubMed PMID: 21961968; PubMed Central PMCID: PMC3196598.

Voth DE, Beare PA, Howe D, Sharma UM, Samoilis G, Cockrell DC, Omsland A, Heinzen RA. The Coxiella burnetii cryptic plasmid is enriched in genes encoding type IV secretion system substrates. J Bacteriol. 2011 Apr;193(7):1493-503. Epub 2011 Jan 7. PubMed PMID: 21216993; PubMed Central PMCID: PMC3067651.

Wahl-Jensen V, Kurz S, Feldmann F, Buehler LK, Kindrachuk J, DeFilippis V, da Silva Correia J, Früh K, Kuhn JH, Burton DR, Feldmann H. Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression. PLoS Negl Trop Dis. 2011 Oct;5(10):e1359. Epub 2011 Oct 18. PubMed PMID: 22028943; PubMed Central PMCID: PMC3196478.

Warawa JM, Long D, Rosenke R, Gardner D, Gherardini FC. Bioluminescent diagnostic imaging to characterize altered respiratory tract colonization by the burkholderia pseudomallei capsule mutant. Front Microbiol. 2011;2:133. Epub 2011 Jun 16. PubMed PMID: 21720539; PubMed Central PMCID: PMC3118415.

White MD, Bosio CM, Duplantis BN, Nano FE. Human body temperature and new approaches to constructing temperature-sensitive bacterial vaccines. Cell Mol Life Sci. 2011 Sep;68(18):3019-31. Epub 2011 May 31. Review. PubMed PMID: 21626408.

Yamashita S, Lukacik P, Barnard TJ, Noinaj N, Felek S, Tsang TM, Krukonis ES, Hinnebusch BJ, Buchanan SK. Structural insights into Ail-mediated adhesion in Yersinia pestis. Structure. 2011 Nov 9;19(11):1672-82. PubMed PMID: 22078566; PubMed Central PMCID: PMC3217190.

Yi Z, Sperzel L, Nürnberger C, Bredenbeek PJ, Lubick KJ, Best SM, Stoyanov CT, Law LM, Yuan Z, Rice CM, MacDonald MR. Identification and characterization of the host protein DNAJC14 as a broadly active flavivirus replication modulator. PLoS Pathog. 2011 Page 185 of 276

Jan 13;7(1):e1001255. PubMed PMID: 21249176; PubMed Central PMCID: PMC3020928.

Zarember KA, Marshall-Batty KR, Cruz AR, Chu J, Fenster ME, Shoffner AR, Rogge LS, Whitney AR, Czapiga M, Song HH, Shaw PA, Nagashima K, Malech HL, Deleo FR, Holland SM, Gallin JI, Greenberg DE. Innate immunity against Granulibacter bethesdensis, an emerging Gram-negative bacterial pathogen. Infect Immun. 2011 Dec 19. [Epub ahead of print] PubMed PMID: 22184421.

Zivcec M, Safronetz D, Haddock E, Feldmann H, Ebihara H. Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus). J Immunol Methods. 2011 May 31;368(1-2):24-35. Epub 2011 Feb 17. PubMed PMID: 21334343; PubMed Central PMCID: PMC3085612.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: NIH RML scientists broadly study pathogens that cause viral hemorrhagic fevers, viral encephalitis, and certain respiratory diseases. This work employs investigations in cell culture; animal models, including nonhuman primates; reservoir species; and arthropod hosts in order to elucidate the viral pathogenesis, immune responses, molecular evolution, cellular and molecular biology, and vector-host interactions. Specifically, studies include pathogenesis and pathophysiology of high-containment pathogens using molecular technologies; immune responses to infection and vaccination of viral pathogens; vector/reservoir transmission of viral pathogens and development of new vaccine candidates; in vitro and in vivo systems to study the interactions between viral pathogens or viral components and host cells; and epidemiology and ecology of pathogens.

Research activities address pathogenesis studies, vaccinology, and development of therapeutic countermeasures and rapid diagnostic assays in support of the civilian biodefense program.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A, B and C Priority Pathogens

• Overlap Select Agents Including NIAID Category A, B and C Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: Page 186 of 276

None

Page 187 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Institutes of Health (NIH), C.W. Bill Young Center for Biodefense and Emerging Infectious Diseases

2. Where is it located (provide both address and geographical location)?

National Institutes of Health, U.S. Department of Health and Human Services 9000 Rockville Pike

Bethesda, Maryland 20892

3. Floor area of laboratory areas by containment level:

BL2 2493 (sqM) BL3 1091 (sqM) BL4 0 (sqM) Total laboratory floor area 3584 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 120

(ii) Division of personnel:

Military 0

Civilian 120

(iii) Division of personnel by category:

Scientists 91

Engineers 0

Technicians 24

Administrative and support staff 5

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Bacteriology Biology Chemistry Immunology Page 188 of 276

Medicine Microbiology Molecular Biology Parasitology Pathogenesis Vaccine Evaluation Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 8

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas: Research $ 36,223,033 Development $ 0 Test and evaluation $ 0 Total $ 36,223,033

(viii) Briefly describe the publication policy of the facility: All researchers are encouraged to publish results in peer-reviewed open literature. The NIH Public Access Policy (http://publicaccess.nih.gov/policy.htm) ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the National Library of Medicine's digital archive PubMed Central upon acceptance for publication. To help advance science and improve human health, the policy requires that these papers are accessible to the public on PubMed Central no later than 12 months after publication.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Altaweel L, Chen Z, Moayeri M, Cui X, Li Y, Su J, Fitz Y, Johnson S, Leppla SH, Purcell R, Eichacker PQ. Delayed treatment with W1-mAb, a chimpanzee-derived monoclonal antibody against protective antigen, reduces mortality from challenges with anthrax edema or lethal toxin in rats and with anthrax spores in mice. Crit Care Med. 2011 Jun;39(6):1439- Page 189 of 276

47. PubMed PMID: 21336113.

Altmann SE, Smith AL, Dyall J, Johnson RF, Dodd LE, Jahrling PB, Paragas J, Blaney JE. Inhibition of cowpox virus and monkeypox virus infection by mitoxantrone. Antiviral Res. 2012 Feb;93(2):305-8. Epub 2011 Dec 11. PubMed PMID: 22182595; PubMed Central PMCID: PMC3272698.

Backus KM, Boshoff HI, Barry CS, Boutureira O, Patel MK, D'Hooge F, Lee SS, Via LE, Tahlan K, Barry CE 3rd, Davis BG. Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Nat Chem Biol. 2011 Apr;7(4):228-35. Epub 2011 Mar 6. PubMed PMID: 21378984; PubMed Central PMCID: PMC3157484.

Banchereau J, Cohn F, Inaba K, Muller B, Mellman I, Nathan C, Nussenzweig M, O'Garra A, Seder B, Schuler G, Sher A. Remembering Ralph Steinman. J Exp Med. 2011 Nov 21;208(12):2343-7. PubMed PMID: 22216461; PubMed Central PMCID: PMC3256974.

Bang H, Park S, Hwang J, Jin H, Cho E, Kim DY, Song T, Shamputa IC, Via LE, Barry CE 3rd, Cho SN, Lee H. Improved rapid molecular diagnosis of multidrug-resistant tuberculosis using a new reverse hybridization assay, REBAMTB-MDR. J Med Microbiol. 2011 Oct;60(Pt 10):1447-54. Epub 2011 May 19. PubMed PMID: 21596910.

Barber DL, Mayer-Barber KD, Feng CG, Sharpe AH, Sher A. CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol. 2011 Feb 1;186(3):1598-607. Epub 2010 Dec 20. PubMed PMID: 21172867.

Barry CE. Lessons from seven decades of antituberculosis drug discovery. Curr Top Med Chem. 2011;11(10):1216-25. PubMed PMID: 21401509.

Barry CS, Backus KM, Barry CE 3rd, Davis BG. ESI-MS assay of M. tuberculosis cell wall antigen 85 enzymes permits substrate profiling and design of a mechanism-based inhibitor. J Am Chem Soc. 2011 Aug 31;133(34):13232-5. Epub 2011 Aug 9. PubMed PMID: 21776980.

Bellanti JA, Lin FY, Chu C, Shiloach J, Leppla SH, Benavides GA, Karpas A, Moayeri M, Guo C, Robbins JB, Schneerson R. Phase 1 Study of a Recombinant Mutant Protective Antigen of Bacillus anthracis. Clin Vaccine Immunol. 2012 Feb;19(2):140-5. Epub 2011 Dec 21. PubMed PMID: 22190398.

Bengali Z, Satheshkumar PS, Yang Z, Weisberg AS, Paran N, Moss B. Drosophila S2 cells are non-permissive for vaccinia virus DNA replication following entry via low pH- dependent endocytosis and early transcription. PLoS One. 2011 Feb 15;6(2):e17248. PubMed PMID: 21347205; PubMed Central PMCID: PMC3039670.

Blaney JE, Wirblich C, Papaneri AB, Johnson RF, Myers CJ, Juelich TL, Holbrook MR, Freiberg AN, Bernbaum JG, Jahrling PB, Paragas J, Schnell MJ. Inactivated or live- Page 190 of 276

attenuated bivalent vaccines that confer protection against rabies and Ebola viruses. J Virol. 2011 Oct;85(20):10605-16. Epub 2011 Aug 17. PubMed PMID: 21849459; PubMed Central PMCID: PMC3187516.

Bray M, Lawler J, Paragas J, Jahrling PB, Mollura DJ. Molecular imaging of influenza and other emerging respiratory viral infections. J Infect Dis. 2011 May 15;203(10):1348-59. Epub 2011 Mar 21. Review. PubMed PMID: 21422476; PubMed Central PMCID: PMC3080905.

Broadbent AJ, Subbarao K. Influenza Virus Vaccines: Lessons from the 2009 H1N1 pandemic. Curr Opin Virol. 2011 Oct;1(4):254-262. PubMed PMID: 22125588; PubMed Central PMCID: PMC3224079.

Chen GL, Lau YF, Lamirande EW, McCall AW, Subbarao K. Seasonal influenza infection and live vaccine prime for a response to the 2009 pandemic H1N1 vaccine. Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1140-5. Epub 2011 Jan 3. PubMed PMID: 21199945; PubMed Central PMCID: PMC3024675.

Chen GL, Min JY, Lamirande EW, Santos C, Jin H, Kemble G, Subbarao K. Comparison of a live attenuated 2009 H1N1 vaccine with seasonal influenza vaccines against 2009 pandemic H1N1 virus infection in mice and ferrets. J Infect Dis. 2011 Apr 1;203(7):930-6. Epub 2011 Jan 21. PubMed PMID: 21257740; PubMed Central PMCID: PMC3068036.

Chen S, Chahar HS, Abraham S, Wu H, Pierson TC, Wang XA, Manjunath N. Ago-2- mediated slicer activity is essential for anti-flaviviral efficacy of RNAi. PLoS One. 2011;6(11):e27551. Epub 2011 Nov 10. PubMed PMID: 22102908; PubMed Central PMCID: PMC3213142.

Cherian J, Choi I, Nayyar A, Manjunatha UH, Mukherjee T, Lee YS, Boshoff HI, Singh R, Ha YH, Goodwin M, Lakshminarayana SB, Niyomrattanakit P, Jiricek J, Ravindran S, Dick T, Keller TH, Dartois V, Barry CE 3rd. Structure-activity relationships of antitubercular nitroimidazoles. 3. Exploration of the linker and lipophilic tail of ((s)-2-nitro-6,7-dihydro- 5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4 trifluoromethoxybenzyl)amine (6-amino PA-824). J Med Chem. 2011 Aug 25;54(16):5639-59. Epub 2011 Jul 26. PubMed PMID: 21755942; PubMed Central PMCID: PMC3158291.

Dowd KA, Jost CA, Durbin AP, Whitehead SS, Pierson TC. A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog. 2011 Jun;7(6):e1002111. Epub 2011 Jun 30. PubMed PMID: 21738473; PubMed Central PMCID: PMC3128118.

Dowd KA, Pierson TC. Antibody-mediated neutralization of flaviviruses: a reductionist view. Virology. 2011 Mar 15;411(2):306-15. Epub 2011 Jan 20. Review. PubMed PMID: 21255816; PubMed Central PMCID: PMC3100196. Page 191 of 276

Duckworth BP, Geders TW, Tiwari D, Boshoff HI, Sibbald PA, Barry CE 3rd, Schnappinger D, Finzel BC, Aldrich CC. Bisubstrate adenylation inhibitors of biotin protein ligase from Mycobacterium tuberculosis. Chem Biol. 2011 Nov 23;18(11):1432-41. PubMed PMID: 22118677; PubMed Central PMCID: PMC3225891.

Dugan VG, Dunham EJ, Jin G, Sheng ZM, Kaser E, Nolting JM, Alexander HL Jr, Slemons RD, Taubenberger JK. Phylogenetic analysis of low pathogenicity H5N1 and H7N3 influenza A virus isolates recovered from sentinel, free flying, wild mallards at one study site during 2006. Virology. 2011 Aug 15;417(1):98-105. Epub 2011 Jun 12. PubMed PMID: 21658737; PubMed Central PMCID: PMC3157087.

Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, Alam F, Noor Z, Verkerke HP, Marie C, Leduc CA, Chua SC Jr, Myers MG Jr, Leibel RL, Houpt E, Dyall J, Johnson RF, Chen DY, Huzella L, Ragland DR, Mollura DJ, Byrum R, Reba RC, Jennings G, Jahrling PB, Blaney JE, Paragas J. Evaluation of monkeypox disease progression by molecular imaging. J Infect Dis. 2011 Dec 15;204(12):1902-11. Epub 2011 Oct 19. PubMed PMID: 22013221; PubMed Central PMCID: PMC3209815.

Easterbrook JD, Dunfee RL, Schwartzman LM, Jagger BW, Sandouk A, Kash JC, Memoli MJ, Taubenberger JK. Obese mice have increased morbidity and mortality compared to non- obese mice during infection with the 2009 pandemic H1N1 influenza virus. Influenza Other Respi Viruses. 2011 Nov;5(6):418-25. doi:10.1111/j.1750-2659.2011.00254.x. Epub 2011 Apr 18. PubMed PMID: 21668672; PubMed Central PMCID: PMC3175349.

Easterbrook JD, Kash JC, Sheng ZM, Qi L, Gao J, Kilbourne ED, Eichelberger MC, Taubenberger JK. Immunization with 1976 swine H1N1- or 2009 pandemic H1N1- inactivated vaccines protects mice from a lethal 1918 influenza infection. Influenza Other Respi Viruses. 2011 May;5(3):198-205. doi:10.1111/j.1750-2659.2010.00191.x. Epub 2011 Jan 25. PubMed PMID: 21477139; PubMed Central PMCID: PMC3073596.

Egen JG, Rothfuchs AG, Feng CG, Horwitz MA, Sher A, Germain RN. Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas. Immunity. 2011 May 27;34(5):807-19. Epub 2011 May 19. PubMed PMID: 21596592; PubMed Central PMCID: PMC3164316.

Esmail H, Barry CE 3rd, Wilkinson RJ. Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies. Drug Discov Today.2011 Dec 20. [Epub ahead of print] PubMed PMID: 22198298.

Frieman M, Yount B, Agnihothram S, Page C, Donaldson E, Roberts A, Vogel L, Woodruff Page 192 of 276

B, Scorpio D, Subbarao K, Baric RS. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J Virol. 2012 Jan;86(2):884-97. Epub 2011 Nov 9. PubMed PMID: 22072787; PubMed Central PMCID: PMC3255850.

Geisbert TW, Bailey M, Hensley L, Asiedu C, Geisbert J, Stanley D, Honko A, Johnson J, Mulangu S, Pau MG, Custers J, Vellinga J, Hendriks J, Jahrling P, Roederer M, Goudsmit J, Koup R, Sullivan NJ. Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J Virol. 2011 May;85(9):4222-33. Epub 2011 Feb 16. PubMed PMID: 21325402; PubMed Central PMCID: PMC3126236.

Gilchrist CA, Sher A, Porcella SF, Petri WA Jr. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. J Clin Invest. 2011 Mar;121(3):1191-8. PubMed PMID: 21393862; PubMed Central PMCID: PMC3049405.

Goepfert PA, Elizaga ML, Sato A, Qin L, Cardinali M, Hay CM, Hural J, DeRosa SC, DeFawe OD, Tomaras GD, Montefiori DC, Xu Y, Lai L, Kalams SA, Baden LR, Frey SE, Blattner WA, Wyatt LS, Moss B, Robinson HL; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2011 Mar 1;203(5):610-9. Epub 2011 Jan 31. PubMed PMID: 21282192; PubMed Central PMCID: PMC3072720.

Gurumurthy M, Mukherjee T, Dowd CS, Singh R, Niyomrattanakit P, Tay JA, Nayyar A, Lee YS, Cherian J, Boshoff HI, Dick T, Barry CE 3rd, Manjunatha UH. Substrate specificity of the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis responsible for the bioreductive activation of bicyclic nitroimidazoles. FEBS J. 2012 Jan;279(1):113-25. doi: 10.1111/j.1742-4658.2011.08404.x. Epub 2011 Nov 14. PubMed PMID: 22023140.

Hicks CW, Li Y, Okugawa S, Solomon SB, Moayeri M, Leppla SH, Mohanty A,Subramanian GM, Mignone TS, Fitz Y, Cui X, Eichacker PQ. Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol. 2011 Mar; 300(3):H1108-18. Epub 2011 Jan 7. PubMed PMID: 21217068; PubMed Central PMCID: PMC3064307.

Hunn JP, Feng CG, Sher A, Howard JC. The immunity-related GTPases in mammals: a fast- evolving cell-autonomous resistance system against intracellular pathogens. Mamm Genome. 2011 Feb;22(1-2):43-54. Epub 2010 Oct 30. Review. PubMed PMID: 21052678.

Johnson RF, Dodd LE, Yellayi S, Gu W, Cann JA, Jett C, Bernbaum JG, Ragland DR, St Claire M, Byrum R, Paragas J, Blaney JE, Jahrling PB. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease. Virology. 2011 Dec 20;421(2):129-40. Epub 2011 Oct Page 193 of 276

19. PubMed PMID: 22014505; PubMed Central PMCID: PMC3210905.

Johnson RF, Yellayi S, Cann JA, Johnson A, Smith AL, Paragas J, Jahrling PB, Blaney JE. Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox. Virology. 2011 Sep 30;418(2):102-12. Epub 2011 Aug 15.PubMed PMID: 21840027; PubMed Central PMCID: PMC3164762.

Kash JC, Walters KA, Davis AS, Sandouk A, Schwartzman LM, Jagger BW, Chertow DS, Li Q, Kuestner RE, Ozinsky A, Taubenberger JK. Lethal synergism of 2009 pandemic H1N1 influenza virus and Streptococcus pneumoniae coinfection is associated with loss of murine lung repair responses. MBio. 2011 Sep 20;2(5).pii: e00172-11. doi: 10.1128/mBio.00172-11. Print 2011. PubMed PMID: 21933918; PubMed Central PMCID: PMC3175626.

Keshtkar-Jahromi M, Kuhn JH, Christova I, Bradfute SB, Jahrling PB, Bavari S. Crimean- Congo hemorrhagic fever: current and future prospects of vaccines and therapies. Antiviral Res. 2011 May;90(2):85-92. Epub 2011 Mar 6. Review. PubMed PMID: 21362441.

Kim S, Jiao GS, Moayeri M, Crown D, Cregar-Hernandez L, McKasson L, Margosiak SA, Leppla SH, Johnson AT. Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy. Bioorg Med Chem Lett. 2011 Apr 1;21(7):2030-3. Epub 2011 Feb 18. PubMed PMID: 21334206; PubMed Central PMCID: PMC3059087.

Kindrachuk J, Arsenault R, Kusalik T, Kindrachuk KN, Trost B, Napper S, Jahrling PB, Blaney JE. Systems kinomics demonstrates congo basin monkeypox virus infection selectively modulates host cell signaling responses as compared to West African monkeypox virus. Mol Cell Proteomics. 2011 Dec 28. [Epub ahead of print] PubMed PMID: 22205724.

Kjellsson MC, Via LE, Goh A, Weiner D, Low KM, Kern S, Pillai G, Barry CE 3rd, Dartois V. Pharmacokinetic evaluation of the penetration of antituberculosis agents in rabbit pulmonary lesions. Antimicrob Agents Chemother. 2012 Jan;56(1):446-57. Epub 2011 Oct 10. PubMed PMID: 21986820; PubMed Central PMCID: PMC3256032.

Kostova MB, Myers CJ, Beck TN, Plotkin BJ, Green JM, Boshoff HI, Barry CE 3rd,Deschamps JR, Konaklieva MI. C4-alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis. Bioorg Med Chem. 2011 Nov 15;19(22):6842- 52. Epub 2011 Oct 1. PubMed PMID: 22014754.

Kuhn JH, Dodd LE, Wahl-Jensen V, Radoshitzky SR, Bavari S, Jahrling PB. Evaluation of perceived threat differences posed by filovirus variants. Biosecur Bioterror. 2011 Dec;9(4):361-71. Epub 2011 Nov 9. PubMed PMID: 22070137; PubMed Central PMCID: PMC3233913. Page 194 of 276

Laassri M, Bidzhieva B, Speicher J, Pletnev AG, Chumakov K. Microarray hybridization for assessment of the genetic stability of chimeric West Nile/dengue 4 virus. J Med Virol. 2011 May;83(5):910-20. doi: 10.1002/jmv.22033. Epub 2011 Feb 25. PubMed PMID: 21360544.

Lai L, Kwa S, Kozlowski PA, Montefiori DC, Ferrari G, Johnson WE, Hirsch V, Villinger F, Chennareddi L, Earl PL, Moss B, Amara RR, Robinson HL. Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine. J Infect Dis. 2011 Jul 1;204(1):164-73. PubMed PMID: 21628671; PubMed Central PMCID: PMC3143670.

Lai L, Kwa SF, Kozlowski PA, Montefiori DC, Nolen TL, Hudgens MG, Johnson WE, Ferrari G, Hirsch VM, Felber BK, Pavlakis GN, Earl PL, Moss B, Amara RR, Robinson HL. SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses. Vaccine. 2012 Feb 21;30(9):1737-45. Epub 2011 Dec 15. PubMed PMID: 22178526; PubMed Central PMCID: PMC3278564.

Lakdawala SS, Lamirande EW, Suguitan AL Jr, Wang W, Santos CP, Vogel L, Matsuoka Y, Lindsley WG, Jin H, Subbarao K. Eurasian-Origin Gene Segments Contribute to the Transmissibility, Aerosol Release, and Morphology of the 2009 Pandemic H1N1 Influenza Virus. PLoS Pathog. 2011 Dec;7(12):e1002443. Epub 2011 Dec 29. PubMed PMID: 22241979; PubMed Central PMCID: PMC3248560.

Laliberte JP, Weisberg AS, Moss B. The membrane fusion step of vaccinia virus entry is cooperatively mediated by multiple viral proteins and host cell components. PLoS Pathog. 2011 Dec;7(12):e1002446. Epub 2011 Dec 15. PubMed PMID: 22194690; PubMed Central PMCID: PMC3240603.

Layre E, Sweet L, Hong S, Madigan CA, Desjardins D, Young DC, Cheng TY, Annand JW, Kim K, Shamputa IC, McConnell MJ, Debono CA, Behar SM, Minnaard AJ, Murray M, Barry CE 3rd, Matsunaga I, Moody DB. A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis. Chem Biol. 2011 Dec 23;18(12):1537-49. PubMed PMID: 22195556.

Ledgerwood JE, Pierson TC, Hubka SA, Desai N, Rucker S, Gordon IJ, Enama ME, Nelson S, Nason M, Gu W, Bundrant N, Koup RA, Bailer RT, Mascola JR, Nabel GJ, Graham BS; VRC 303 Study Team. A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial. J Infect Dis. 2011 May 15;203(10):1396-404. Epub 2011 Mar 11. PubMed PMID: 21398392; PubMed Central PMCID: PMC3080891.

Leysath CE, Chen KH, Moayeri M, Crown D, Fattah R, Chen Z, Das SR, Purcell RH, Leppla SH. Mouse monoclonal antibodies to anthrax edema factor protect against infection. Infect Immun. 2011 Nov;79(11):4609-16. Epub 2011 Sep 12. PubMed PMID: 21911463; Page 195 of 276

PubMed Central PMCID: PMC3257937.

Manier ML, Reyzer ML, Goh A, Dartois V, Via LE, Barry CE 3rd, Caprioli RM. Reagent precoated targets for rapid in-tissue derivatization of the anti-tuberculosis drug isoniazid followed by MALDI imaging mass spectrometry. J Am Soc Mass Spectrom. 2011 Aug;22(8):1409-19. Epub 2011 May 13. PubMed PMID: 21953196.

Marthas ML, Van Rompay KK, Abbott Z, Earl P, Buonocore-Buzzelli L, Moss B, Rose NF, Rose JK, Kozlowski PA, Abel K. Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques. Vaccine. 2011 Apr 12;29(17):3124-37. Epub 2011 Mar 4. PubMed PMID: 21377510; PubMed Central PMCID: PMC3078946.

Maruri-Avidal L, Domi A, Weisberg AS, Moss B. Participation of vaccinia virus l2 protein in the formation of crescent membranes and immature virions. J Virol. 2011 Mar;85(6):2504-11. Epub 2011 Jan 12. PubMed PMID: 21228235; PubMed Central PMCID: PMC3067936.

Maruri-Avidal L, Weisberg AS, Moss B. Vaccinia virus L2 protein associates with the endoplasmic reticulum near the growing edge of crescent precursors of immature virions and stabilizes a subset of viral membrane proteins. J Virol. 2011 Dec;85(23):12431-41. Epub 2011 Sep 14. PubMed PMID: 21917978; PubMed Central PMCID: PMC3209352.

Mashalidis EH, Mukherjee T, Sledź P, Matak-Vinković D, Boshoff H, Abell C, Barry CE 3rd. Rv2607 from Mycobacterium tuberculosis is a pyridoxine 5'-phosphate oxidase with unusual substrate specificity. PLoS One. 2011;6(11):e27643. Epub 2011 Nov 14. PubMed PMID: 22110704; PubMed Central PMCID: PMC3215729.

Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A, Goldszmid RS, Sher A, Ploegh HL, Murphy TL, Sibley LD, Murphy KM. CD8Î±(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity. 2011 Aug 26;35(2):249-59. PubMed PMID: 21867928; PubMed Central PMCID: PMC3171793.

Mayer-Barber KD, Andrade BB, Barber DL, Hieny S, Feng CG, Caspar P, Oland S, Gordon S, Sher A. Innate and adaptive interferons suppress IL-1Î± and IL-1Î² production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection. Immunity. 2011 Dec 23;35(6):1023-34. PubMed PMID:22195750; PubMed Central PMCID: PMC3246221.

Mehle A, Dugan VG, Taubenberger JK, Doudna JA. Reassortment and Mutation of the Avian Influenza Virus Polymerase PA Subunit Overcome Species Barriers. J Virol. 2012 Feb;86(3):1750-7. Epub 2011 Nov 16. PubMed PMID: 22090127; PubMed Central PMCID: PMC3264373.

Moayeri M, Sastalla I, Leppla SH. Anthrax and the inflammasome. Microbes Infect. 2011 Page 196 of 276

Dec 17. [Epub ahead of print] PubMed PMID: 22207185.

Morens DM, Holmes EC, Davis AS, Taubenberger JK. Global rinderpest eradication: lessons learned and why humans should celebrate too. J Infect Dis. 2011 Aug 15;204(4):502-5. Epub 2011 Jun 7. PubMed PMID: 21653230; PubMed Central PMCID: PMC3144172.

Morens DM, Taubenberger JK. Pandemic influenza: certain uncertainties. Rev Med Virol. 2011 Jun 27. doi: 10.1002/rmv.689. [Epub ahead of print] PubMed PMID: 21706672; PubMed Central PMCID: PMC3246071.

Moss B. Smallpox vaccines: targets of protective immunity. Immunol Rev. 2011 Jan;239(1):8-26. doi: 10.1111/j.1600-065X.2010.00975.x. Review. PubMed PMID: 21198662; PubMed Central PMCID: PMC3074351.

Mukherjee S, Lin TY, Dowd KA, Manhart CJ, Pierson TC. The infectivity of prM- containing partially mature West Nile virus does not require the activity of cellular furin-like proteases. J Virol. 2011 Nov;85(22):12067-72. Epub 2011 Aug 31. PubMed PMID: 21880759; PubMed Central PMCID: PMC3209279.

Mukherjee T, Boshoff H, Barry CE 3rd. Comment on: Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae. J Antimicrob Chemother. 2012 Jan;67(1):252-3. Epub 2011 Oct 7. PubMed PMID: 21984744; PubMed Central PMCID: PMC3236054.

Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011 Jul 10;12(8):786-95. doi: 10.1038/ni.2067. PubMed PMID: 21743478; PubMed Central PMCID: PMC3140559.

Novikov A, Cardone M, Thompson R, Shenderov K, Kirschman KD, Mayer-Barber KD, Myers TG, Rabin RL, Trinchieri G, Sher A, Feng CG. Mycobacterium tuberculosis triggers host type I IFN signaling to regulate IL-1Î² production in human macrophages. J Immunol. 2011 Sep 1;187(5):2540-7. Epub 2011 Jul 22. PubMed PMID: 21784976; PubMed Central PMCID: PMC3159798.

O'Donnell CD, Subbarao K. The contribution of animal models to the understanding of the host range and virulence of influenza A viruses. Microbes Infect. 2011 May;13(5):502-15. Epub 2011 Jan 27. Review. PubMed PMID: 21276869; PubMed Central PMCID: PMC3071864.

Okugawa S, Moayeri M, Pomerantsev AP, Sastalla I, Crown D, Gupta PK, Leppla SH. Lipoprotein biosynthesis by prolipoprotein diacylglyceryl transferase is required for efficient spore germination and full virulence of Bacillus anthracis. Mol Microbiol. 2012 Page 197 of 276

Jan;83(1):96-109. doi: 10.1111/j.1365-2958.2011.07915.x. Epub 2011 Nov 22. PubMed PMID: 22103323; PubMed Central PMCID: PMC3245379.

Ou W, Delisle J, Konduru K, Bradfute S, Radoshitzky SR, Retterer C, Kota K, Bavari S, Kuhn JH, Jahrling PB, Kaplan G, Wilson CA. Development and characterization of rabbit and mouse antibodies against ebolavirus envelope glycoproteins. J Virol Methods. 2011 Jun;174(1-2):99-109. Epub 2011 Apr 13. PubMed PMID: 21513741; PubMed Central PMCID: PMC3106979.

Pomerantsev AP, Pomerantseva OM, Moayeri M, Fattah R, Tallant C, Leppla SH. A Bacillus anthracis strain deleted for six proteases serves as an effective host for production of recombinant proteins. Protein Expr Purif. 2011 Nov;80(1):80-90. Epub 2011 Aug 7. PubMed PMID: 21827967; PubMed Central PMCID: PMC3183367.

Radoshitzky SR, Warfield KL, Chi X, Dong L, Kota K, Bradfute SB, Gearhart JD, Retterer C, Kranzusch PJ, Misasi JN, Hogenbirk MA, Wahl-Jensen V, Volchkov VE, Cunningham JM, Jahrling PB, Aman MJ, Bavari S, Farzan M, Kuhn JH. Ebolavirus delta-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry. J Virol. 2011 Sep;85(17):8502-13. Epub 2011 Jun 22. PubMed PMID: 21697477; PubMed Central PMCID: PMC3165852.

Sastalla I, Leppla SH. Occurrence, recognition, and reversion of spontaneous, sporulation- deficient Bacillus anthracis mutants that arise during laboratory culture. Microbes Infect. 2011 Nov 28. [Epub ahead of print] PubMed PMID: 22166343.

Sastalla I, Tang S, Crown D, Liu S, Eckhaus MA, Hewlett IK, Leppla SH, Moayeri M. Anthrax edema toxin impairs clearance in mice. Infect Immun. 2012 Feb;80(2):529-38. Epub 2011 Nov 21. PubMed PMID: 22104108; PubMed Central PMCID: PMC3264307.

Satheshkumar PS, Moss B. Sequence-divergent chordopoxvirus homologs of the o3 protein maintain functional interactions with components of the vaccinia virus entry-fusion complex. J Virol. 2012 Feb;86(3):1696-705. Epub 2011 Nov 23. PubMed PMID: 22114343; PubMed Central PMCID: PMC3264392.

Schafer JM, Peters DE, Morley T, Liu S, Molinolo AA, Leppla SH, Bugge TH. Efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual uPA and MMP-activated engineered anthrax toxin. PLoS One. 2011;6(5):e20532. Epub 2011 May 31. PubMed PMID: 21655226; PubMed Central PMCID: PMC3105081.

Schwartz JA, Buonocore L, Suguitan A Jr, Hunter M, Marx PA, Subbarao K, Rose JK. Vesicular stomatitis virus-based H5N1 avian influenza vaccines induce potent cross-clade neutralizing antibodies in rhesus macaques. J Virol. 2011 May;85(9):4602-5. Epub 2011 Feb 16. PubMed PMID: 21325423; PubMed Central PMCID: PMC3126271.

Senkevich TG, Koonin EV, Moss B. Vaccinia virus F16 protein, a predicted catalytically Page 198 of 276

inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli. Virology. 2011 Sep 1;417(2):334-42. Epub 2011 Jul 12. PubMed PMID: 21752417; PubMed Central PMCID: PMC3163719.

Sheng ZM, Chertow DS, Ambroggio X, McCall S, Przygodzki RM, Cunningham RE, Maximova OA, Kash JC, Morens DM, Taubenberger JK. Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16416-21. Epub 2011 Sep 19. PubMed PMID: 21930918; PubMed Central PMCID: PMC3182717.

Shi C, Geders TW, Park SW, Wilson DJ, Boshoff HI, Abayomi O, Barry CE 3rd, Schnappinger D, Finzel BC, Aldrich CC. Mechanism-based inactivation by aromatization of the transaminase BioA involved in biotin biosynthesis in Mycobaterium tuberculosis. J Am Chem Soc. 2011 Nov 16;133(45):18194-201. Epub 2011 Oct 24. PubMed PMID: 21988601; PubMed Central PMCID: PMC3222238.

Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. Epub 2011 Aug 11. PubMed PMID: 21835980.

Shui G, Bendt AK, Jappar IA, Lim HM, Laneelle M, Hervé M, Via LE, Chua GH, Bratschi MW, Rahim SZ, Michelle AL, Hwang SH, Lee JS, Eum SY, Kwak HK, Daffé M, Dartois V, Michel G, Barry CE 3rd, Wenk MR. Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice. EMBO Mol Med. 2012 Jan;4(1):27-37. doi: 10.1002/emmm.201100185. Epub 2011 Dec 7. PubMed PMID: 22147526.

Sitaraman R, Leppla SH. Methylation-dependent DNA restriction in Bacillus anthracis. Gene. 2012 Feb 15;494(1):44-50. Epub 2011 Dec 8. PubMed PMID: 22178763; PubMed Central PMCID: PMC3265652.

Smith AL, St Claire M, Yellayi S, Bollinger L, Jahrling PB, Paragas J, Blaney JE, Johnson RF. Intrabronchial inoculation of cynomolgus macaques with cowpox virus. J Gen Virol. 2012 Jan;93(Pt 1):159-64. Epub 2011 Sep 21. PubMed PMID: 21940414.

Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med. 2011 Aug 21;17(9):1128-31. doi: 10.1038/nm.2447. PubMed PMID: 21857654.

Suguitan AL Jr, Matsuoka Y, Lau YF, Santos CP, Vogel L, Cheng LI, Orandle M, Subbarao K. The Multibasic Cleavage Site of the Hemagglutinin of Highly Pathogenic A/Vietnam/1203/2004 (H5N1) Avian Influenza Virus Acts as a Virulence Factor in a Host- Specific Manner in Mammals. J Virol. 2012 Mar;86(5):2706-14. Epub 2011 Dec 28. Page 199 of 276

PubMed PMID: 22205751.

Talaat KR, Karron RA, Luke CJ, Thumar B, McMahon BA, Chen GL, Lamirande EW, Jin H, Coelingh KL, Kemble G, Subbarao K. An open label Phase I trial of a live attenuated H6N1 influenza virus vaccine in healthy adults. Vaccine. 2011 Apr 12;29(17):3144-8. Epub 2011 Mar 4. PubMed PMID: 21377509; PubMed Central PMCID: PMC3105354.

Vogt MR, Dowd KA, Engle M, Tesh RB, Johnson S, Pierson TC, Diamond MS. Poorly neutralizing cross-reactive antibodies against the fusion loop of West Nile virus envelope protein protect in vivo via Fcgamma receptor and complement-dependent effector mechanisms. J Virol. 2011 Nov;85(22):11567-80. Epub 2011 Sep 14. PubMed PMID: 21917960; PubMed Central PMCID: PMC3209272.

Wahl-Jensen V, Cann JA, Rubins KH, Huggins JW, Fisher RW, Johnson AJ, de Kok- Mercado F, Larsen T, Raymond JL, Hensley LE, Jahrling PB. Progression of pathogenic events in cynomolgus macaques infected with variola virus. PLoS One.2011;6(10):e24832. Epub 2011 Oct 6. PubMed PMID: 21998632; PubMed Central PMCID: PMC3188545.

Wang R, Schwartzman LM, Memoli MJ, Taubenberger JK. Detection of seasonal H3N2 influenza A virus by type-specific TaqMan minor groove binder probe assay. Diagn Microbiol Infect Dis. 2011 Jun;70(2):281-4. Epub 2011 Mar 22. PubMed PMID: 21429691; PubMed Central PMCID: PMC3164769.

Wang Z, Lai Y, Bernard JJ, Macleod DT, Cogen AL, Moss B, Di Nardo A. Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides. J Immunol. 2012 Jan 1;188(1):345-57. Epub 2011 Dec 2. PubMed PMID: 22140255; PubMed Central PMCID: PMC3244574.

Watanabe S, Zimmermann M, Goodwin MB, Sauer U, Barry CE 3rd, Boshoff HI. Fumarate reductase activity maintains an energized membrane in anaerobic Mycobacterium tuberculosis. PLoS Pathog. 2011 Oct;7(10):e1002287. Epub 2011 Oct 6. PubMed PMID: 21998585; PubMed Central PMCID: PMC3188519.

Wise HM, Barbezange C, Jagger BW, Dalton RM, Gog JR, Curran MD, Taubenberger JK, Anderson EC, Digard P. Overlapping signals for translational regulation and packaging of influenza A virus segment 2. Nucleic Acids Res. 2011 Sep 1;39(17):7775-90. Epub 2011 Jun 21. PubMed PMID: 21693560; PubMed Central PMCID: PMC3177217.

Wong SY, Lee JS, Kwak HK, Via LE, Boshoff HI, Barry CE 3rd. Mutations in gidB confer low-level streptomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2011 Jun;55(6):2515-22. Epub 2011 Mar 28. PubMed PMID: 21444711; PubMed Central PMCID: PMC3101441.

Woong Park S, Klotzsche M, Wilson DJ, Boshoff HI, Eoh H, Manjunatha U, Blumenthal A, Rhee K, Barry CE 3rd, Aldrich CC, Ehrt S, Schnappinger D. Evaluating the sensitivity of Page 200 of 276

Mycobacterium tuberculosis to biotin deprivation using regulated gene expression. PLoS Pathog. 2011 Sep;7(9):e1002264. Epub 2011 Sep 29. PubMed PMID: 21980288; PubMed Central PMCID: PMC3182931.

Wolfe CL, Moss B. Interaction between the G3 and L5 proteins of the vaccinia virus entry- fusion complex. Virology. 2011 Apr 10;412(2):278-83. Epub 2011 Feb 4. PubMed PMID: 21295816; PubMed Central PMCID: PMC3073817.

Wolfe CL, Ojeda S, Moss B. Transcriptional repression and RNA silencing act synergistically to demonstrate the function of the eleventh component of the vaccinia virus entry-fusion complex. J Virol. 2012 Jan;86(1):293-301. Epub 2011 Oct 19. PubMed PMID: 22013036; PubMed Central PMCID: PMC3255872.

Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O'Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med. 2011 Jan 17;208(1):181-93. Epub 2011 Jan 10. Erratum in: J Exp Med. 2011 Feb 14;208(2):411. PubMed PMID: 21220454; PubMed Central PMCID: PMC3023136.

Yang Z, Bruno DP, Martens CA, Porcella SF, Moss B. Genome-wide analysis of the 5' and 3' ends of vaccinia virus early mRNAs delineates regulatory sequences of annotated and anomalous transcripts. J Virol. 2011 Jun;85(12):5897-909. Epub 2011 Apr 13. PubMed PMID: 21490097; PubMed Central PMCID: PMC3126295.

Yang Z, Reynolds SE, Martens CA, Bruno DP, Porcella SF, Moss B. Expression profiling of the intermediate and late stages of poxvirus replication. J Virol. 2011 Oct;85(19):9899- 908. Epub 2011 Jul 27. PubMed PMID: 21795349; PubMed Central PMCID: PMC3196450.

Qi L, Kash JC, Dugan VG, Jagger BW, Lau YF, Sheng ZM, Crouch EC, Hartshorn KL, Taubenberger JK. The ability of pandemic influenza virus hemagglutinins to induce lower respiratory pathology is associated with decreased surfactant protein D binding. Virology. 2011 Apr 10;412(2):426-34. Epub 2011 Feb 18. PubMed PMID: 21334038; PubMed Central PMCID: PMC3060949.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: At the C.W. Bill Young Center for Biodefense and Emerging Infectious Diseases, the Laboratory of Infectious Diseases (LID) focuses on viral vaccine development, host immune response to viruses, and viral molecular biology and genetics. Newer programs focus on Page 201 of 276

developing vaccines, from basic research to clinical trials.

The Laboratory of Bacterial Diseases (LBD) focuses on the development of diagnostics, vaccines, and therapeutics for biodefense. Specifc research concerns the identification and analysis of bacterial virulence factors and their genetic regulation; structure-function analysis of bacterial proteins and other factors; disease pathogenesis.

The Laboratory of Viral Diseases (LVD) studies the basic mechanisms of viral entry into cells, regulation of viral gene expression, viral DNA replication, assembly and transport of viral proteins and particles, viral virulence, and humoral and cellular immunity, for DNA and RNA viruses. Applied research includes development of recombinant expression vectors, candidate vaccines, and antiviral agents.

(ii) Agents Microorganisms and/or Toxins:

• HHS Select Agents and Toxins Including NIAID Category A and B Priority Pathogens

• Overlap Select Agents Including NIAID Category A Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category A, B and C Priority Pathogens

(iii) Outdoor Studies: None

Page 202 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Institutes of Health (NIH), Dale and Betty Bumpers Vaccine Research Center

2. Where is it located (provide both address and geographical location)?

National Institutes of Health, US Department of Health and Human Services 9000 Rockville Pike

Bethesda, Maryland 20892

3. Floor area of laboratory areas by containment level:

BL2 89 (sqM) BL3 0 (sqM) BL4 0 (sqM) Total laboratory floor area 89 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 8

(ii) Division of personnel:

Military 0

Civilian 8

(iii) Division of personnel by category:

Scientists 8

Engineers 0

Technicians 0

Administrative and support staff 0

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Biology Chemistry Immunology Microbiology Molecular Biology Page 203 of 276

Pathogenesis Vaccine Evaluation Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 2

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Health and Human Services (HHS)

(vii) What are the funding levels for the following program areas: Research $ 774,548 Development $ 0 Test and evaluation $ 0 Total $ 774,548

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Fabozzi G, Nabel CS, Dolan MA, Sullivan NJ. Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway. J Virol. 2011 Mar;85(6):2512-23. Epub 2011 Jan 12. PubMed PMID: 21228243; PubMed Central PMCID: PMC3067942.

challenge. J Virol. 2011 May;85(9):4222-33. Epub 2011 Feb 16. PubMed PMID: 21325402; PubMed Central PMCID: PMC3126236.

Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med. 2011 Aug 21;17(9):1128-31. doi: 10.1038/nm.2447. PubMed PMID: 21857654.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The research focus of the Biodefense Research Laboratory, Vaccine Research Center (VRC) comprises three areas:

1. Development of vaccines and antivirals 2. Studies of the mechanism of vaccine-induced immune protection 3. Basic research to understand the mechanism of virus replication (entry) and neutralization

(ii) Agents Microorganisms and/or Toxins:

• Other pathogens or toxins

(iii) Outdoor Studies: None

Page 205 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Foreign Disease-Weed Science Research Unit

2. Where is it located (provide both address and geographical location)?

1301 Ditto Avenue Fort Detrick, Maryland 21702

3. Floor area of laboratory areas by containment level:

BL2 105 (sqM) BL3 950 (sqM) BL4 0 (sqM) Total laboratory floor area 1055 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 36

(ii) Division of personnel:

Military 0

Civilian 36

(iii) Division of personnel by category:

Scientists 13

Engineers 0

Technicians 16

Administrative and support staff 7

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Agronomy Biological Control Horticulture Plant Biochemistry Plant Molecular Biology Plant Pathology Page 206 of 276

Plant Physiology Plant Virology Weed Science

(v) Are contractor staff working in the facility? If so, provide an approximate number.

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA)

(vii) What are the funding levels for the following program areas: Research $ 5,600,000 Development $ 0 Test and evaluation $ 0 Total $ 5,600,000

(viii) Briefly describe the publication policy of the facility: All scientific research data is available for publication in peer-reviewed publications after review for dual use determination. All scientists are required to have minimum of two peer- reviewed publications per year. They are encouraged to present research at scientific conferences and publish in books and proceedings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Berner, D.K., Cavin, C.A. 2011. Finalizing host range determination of a weed biological control pathogen with BLUPs and damage assessment. Biocontrol. DOI:10.1007/S10526- 011-9399-X.

Brlansky, R.H., Avijit, R., Damsteegt, V.D. 2011. Stem pitting Citrus tristeza virus predominantly transmitted by the brown citrus aphid from mixed infections containing non- stem pitting and stem pitting isolates. Plant Disease. 95:913-920.

Bruckart, W.L., Eskandari, F., Widmer, T.L. 2011. Synchytrium solstitiale: reclassification based on the function and role of resting spores. Mycologia. DOI: 10.3852/10-286. Page 207 of 276

Damsteegt, V.D., Stone, A.L., Kuhlmann, M., Gildow, F.E., Domier, L.L., Sherman, D.J., Tian, B., Schneider, W.L. 2011. Acquistion and transmissibility of United States Soybean dwarf virus isolates by the soybean aphid Aphis glycines. Plant Disease. 95: 945-950.

Edwards, H.H., Bonde, M.R. 2011. Penetration and establishment of Phakopsora pachyrhizi in soybean leaves as observed by transmission electron microscopy. Phytopathology. 101:894-900.

Eskandari, F., Bruckart, W.L., Widmer, T.L. 2011. Field damage to yellow starthistle infected by Synchytrium solstitiale, and greenhouse maintenance and host range of the fungus. Plant Disease. DOI: 10.1094/PDis-2-11-0139.

Kendrick, M.D., Harris, D.K., Ha, B., Hyten, D.L., Cregan, P.B., Frederick, R.D., Boema, H.R., Pedley, K.F. 2011. Identification of a second Asian soybean rust resistance gene in Hyuuga soybean. Phytopathology. 101:535-543.

Li, P., Feng, B., Wang, H., Tooley, P.W., Zhang, X. 2011. Isolation of nine Phytophthora capsici pectin methylesterase genes which are differentially expressed in various plant species. Journal of Basic Microbiology. 51:61-70.

Schneider, W.L., Damsteegt, V.D., Gildow, F.E., Stone, A.L., Sherman, D.J., Levy, L.E., Mavrodieva, V., Richwine, N., Welliver, R., Luster, D.G. 2011. Molecular, ultrastructural and biological characterization of Pennsylvania isolates of plum pox potyvirus (PPV). Phytopathology. 94:528-533.

Schneider, W.L., Damsteegt, V.D., Stone, A.L., Kuhlman, M., Bunyard, B., Sherman, D.J., Graves, M., Smythers, G., Smith, O., Hatziloukas, E. 2011. Molecular analysis of Soybean dwarf virus isolates in the eastern United States confirms the presence of both D and Y strains and provides evidence of mixed infections and recombination. Virology. 412: 46-54.

Schneider, K.T., Van De Mortel, M., Bancroft, T.J., Nelson, R., Nettleton, D., Braun, E., Frederick, R.D., Baum, T.J., Graham, M.A., Whitham, S.A. 2011. Biphasic gene expression changes elicited by Phakopsora pachyrhizi in soybean correlates with fungal penetration and haustoria formation. Plant Physiology. 157:355-371.

Tooley, P.W., Browning, M.E., Leighty, R.M. 2011. Infectivity and sporulation of Phytophthora ramorum on northern red oak and chestnut oak. Journal of Phytopathology. 159:516-521.

Tooley, P.W., Carras, M.M. 2011. Enhanced recovery of Phytophthora ramorum from soil following 30 days storage at 4C. Journal of Phytopathology. 159:641-643.

Twizeyimana, M., Ojiambo, P.S., Haudenshield, J.S., Caetano-Anolles, G., Pedley, K.F., Bandyopadhyay, R., Hartman, G.L. 2011. Genetic diversity and structure of Phakopsora Page 208 of 276

pachyrhizi infecting soybean in Nigeria. Phytopathology. 60:719-729.

Widmer, T.L. 2011. Survival of Phytophthora kernoviae oospores, sporangia, and mycelium. New Zealand Journal of Forestry Science. 41S:S15-S23.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: The USDA, Agricultural Research Service, Foreign Disease-Weed Science Research Unit has two distinct missions united by a common relationship to plant pathology and the unit's unique BL-3 plant pathogen laboratory and greenhouse containment facilities.

The mission of the foreign disease program is to develop techniques for the rapid detection and identification of new and emerging crop pathogens, and to provide fundamental information on emerging pathogens for risk assessment and the development of practical phytosanitary regulations for the import and export of agricultural commodities and germplasm.

The mission of the weed biological control program is to collect foreign pathogens overseas from weeds in their native habitat, and to evaluate, characterize and release the pathogens in the U.S. for biological control of introduced weeds, leading to improved, sustainable weed control practices in agricultural systems with reduced dependence on chemical herbicides.

(ii) Agents Microorganisms and/or Toxins:

• USDA Plant Protection and Quarantine (PPQ) Select Agents and Toxins • Other pathogens or toxins

The agents studied are foreign and/or emerging pathogens of plants that have an agricultural base. The agents studied include viruses, bacteria, and fungi. The majority of the agents studied are not classified by USDA as select agents. The agents classified as select agents are pathogens that pose a threat to our plant production systems, our agricultural economy, and exports.

(iii) Outdoor Studies: None

Page 209 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

National Animal Disease Center (NADC)

2. Where is it located (provide both address and geographical location)?

1920 Dayton Avenue Ames, Iowa 50010

3. Floor area of laboratory areas by containment level:

BL2 4410 (sqM) BL3 2489 (sqM) BL4 0 (sqM) Total laboratory floor area 6899 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 282

(ii) Division of personnel:

Military 0

Civilian 282

(iii) Division of personnel by category:

Scientists 46

Engineers 0

Technicians 80

Administrative and support staff 156

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Agricultural Engineering Animal Science Biochemistry Bioinformatics Biology Biotechnology Page 210 of 276

Cell Biology Clinical Immunology Computational Biology Ecology Genetics Genomics Immunology Infectious Disease Mass Spectrometry Mass Spectrometry Biochemistry Microbiology Molecular Biology Pathogenesis Pathology Physiology Prionology Proteomics Statistics Structural Biology Vaccine Evaluation Veterinary Clinical Research Veterinary Medicine Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 5

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA) Department of Defense - partly Department of Health and Human Services (DHHS) Private Sector Companies Non-profit Associations Universities Other Governmental Agencies

(vii) What are the funding levels for the following program areas:

Research $ 32,000,000 Page 211 of 276

Development $ 0 Test and evaluation $ 0 Total $ 32,000,000

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Chen, L.M., Rivailler, P., Hossain, J.M., Carney, P., Balish, A., Perry, I., Davis, C.T., Garten, R., Shu, B., Xu, X., Klimov, A., Paulson, J.C., Cox, N.J., Swenson, S., Stevens, J., Vincent, A., Gramer, M., Donis, R.O. 2011. Receptor specificity of subtype H1 influenza A viruses isolated from swine and humans in the United States. Virology. 412(2):401-410.

Gauger, P.C., Vincent, A.L., Loving, C.L., Lager, K.M., Janke, B.H., Kehrli, Jr., M.E., Roth, J.A. 2011. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human- like (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus. Vaccine. 29(15):2712-2719.

Gorres, J.P., Lager, K.M., Kong, W.P., Royals, M., Todd, J.P., Vincent, A.L., Wei, C.J., Loving, C.L., Zanella, E.L., Janke, B., Kehrli, Jr., M.E., Nabel, G.J., Rao, S.S. 2011. DNA vaccination elicits protective immune responses against pandemic and classic swine influenza viruses in pigs. Clinical and Vaccine Immunology. 18(11):1987-1995.

Greenlee, J.J., Smith, J.D., Kunkle, R.A. 2011. White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation. Veterinary Research. 42(1):107.

Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A., Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting disease (CWD) from elk and white- tailed deer to fallow deer by intracerebral route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.

Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith, J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E. 2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME). Canadian Journal of Veterinary Research. 75(1):18-24.

Ivanov, A.V., Salmakov, K.M., Olsen, S.C., Plumb, G.E. 2011. A live vaccine from Page 212 of 276

Brucella abortus strain 82 for control of cattle brucellosis in the Russian Federation. Animal Health Research Reviews. 12(1):113-121.

Kitikoon, P., Sreta, D., Nuntawan Na Ayudhya, S., Wongphatcharachai, M., Lapkuntod, J., Prakairungnamthip, D., Bunpapong, N., Suradhat, S., Thanawongnuwech, R., Amonsin, A. 2011. Brief report: molecular characterization of a novel reassorted pandemic H1N1 2009 in Thai pigs. Virus Genes. 43(1):1-5.

Larson, L.J., Henningson, J., Sharp, P., Thiel, B., Deshpande, M.S., Davis, T., Jayappa, H., Wasmoen, T., Lakshmanan, N., Schultz, R.D. 2011. Efficacy of canine influenza virus (H3N8) vaccine to decrease severity of clinical disease after cochallenge with canine influenza virus and Streptococcus equi subsp. Zooepidemicus. Clinical and Vaccine Immunology. 18(4):559-564.

Lorusso, A., Vincent, A.L., Harland, M.L., Alt, D., Bayles, D.O., Swenson, S.L., Gramer, M.R., Russel, C.A., Smith, D.J., Lager, K.M., Lewis, N.S. 2011. Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008. Journal of General Virology. 92(Pt 4):919-930.

Nelson, M.I., Lemey, P., Tan, Y., Vincent, A., Lam, T.T-Y., Detmer, S., Viboud, C., Suchard, M.A., Rambaut, A., Holmes, E.C., Gramer, M. 2011. Spatial dynamics of human- origin H1 influenza A virus in North American swine. PLoS Pathogens. 7(6):e1002077.

Nfon, C.K., Berhane, Y., Hisanaga, T., Zhang, S., Handel, K., Kehler, H., Labrecque, O., Lewis, N.S., Vincent, A.L., Copps, J., Alexandersen, S., Pasick, J. 2011. Characterization of H1N1 swine influenza viruses circulating in Canadian pigs in 2009. Journal of Virology. 85(17):8667-8679.

Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot. Journal of Veterinary Diagnostic Investigation. 23(4):790- 792.

Nicholson, E.M., Greenlee, J.J., Hamir, A.N. 2011. PrPSc detection in formalin-fixed paraffinembedded tissue by ELISA. BMC Research Notes. 4(1):432.

Nicholson, T.L., Kukielka, D., Vincent, A.L., Brockmeier, S.L., Miller, L.C., Faaberg, K.S. 2011. Utility of a panviral microarray for detection of swine respiratory viruses in clinical samples. Journal of Clinical Microbiology. 49(4):1542-1548.

Olsen, S.C., Johnson, C.S. 2011. Comparison of abortion and infection after experimental challenge of pregnant bison and cattle with Brucella abortus strain 2308. Clinical and Vaccine Immunology. 18(12):2075-2078.

Pena, L., Vincent, A.L., Ye, J., Ciacci-Zanella, J.R., Angel, M., Lorusso, A., Gauger, P.C., Janke, B.H., Loving, C.L., Perez, D.R. 2011. Modifications in the polymerase genes of a Page 213 of 276

swinelike triple reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 Viruses. Journal of Virology. 85(1):456-469.

Pena, L., Vincent, A.L., Ye, J., Ciacci-Zanella, J.E., Angel, M., Lorusso, A., Gauger, P.C., Janke, B.H., Loving, C.L., Perez, D.R. 2011. Safety and efficacy of a novel live attenuated influenza vaccine against pandemic H1N1 in swine. Influenza and Other Respiratory Viruses. 5(S1):341-344.

Platt, R., Vincent, A.L., Gauger, P.C., Loving, C.L., Zanella, E.L., Lager, K.M., Kehrli, Jr., M.E., Kimura, K., Roth, J.A. 2011. Comparison of humoral and cellular immune responses to inactivated swine influenza virus vaccine in weaned pigs. Veterinary Immunology and Immunopathology. 142(3-4):252-257.

Porcario, C., Hall, S.M., Martucci, F., Corona, C., Iulini, B., Perazzini, A.Z., Acutis, P., Hamir, A.N., Loiacono, C.M., Greenlee, J.J., Richt, J.A., Caramelli, M., Casalone, C. 2011. Evaluation of two sets of immunohistochemical and Western blot confirmatory methods in the detection of typical and atypical BSE cases. BMC Research Notes. 4:376.

Schaefer, R., Zanella, J.R.C., Brentano, L., Vincent, A.L., Ritterbusch, G.A., Silveira, S., Caron, L., Mores, N. 2011. Isolation and characterization of pandemic H1N1 influenza viruses in pigs in Brazil. Pesquisa Veterinaria Brasileira. 31(9):761-767.

Shao, H., Ye, J., Vincent, A.L., Edworthy, N., Ferrero, A., Qin, A., Perez, D. 2011. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice. Virology. 417(2):379-384.

Thontiravong, A., Tantilertcharoen, R., Tuanudom, R., Sreta, D., Thanawongnuwech, R., Amonsin, A., Oraveerakul, K., Kitikoon, P. 2011. Single-step multiplex reverse transcription-polymerase chain reaction assay for detection and differentiation of the 2009 (H1N1) influenza A virus pandemic in Thai swine populations. Journal of Veterinary Diagnostic Investigation. 23(5):1017-1021.

Wisedchanwet, T., Wongphatcharachai, M., Boonyapisitsopa, S., Bunpapong, N., Kitikoon, P., Amonsin, A. 2011. Genetic characterization of avian influenza subtype H4N6 and H4N9 from live bird market, Thailand. Virology Journal. 8:131.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Provide scientific information to solutions in the control and eradication of national and international exotic, emerging, zoonotic, and endemic infectious diseases of animals through

a comprehensive research program emphasizing basic and applied research in diagnostics, prevention, and control strategies, prediction of disease outbreaks, molecular epidemiology, Page 214 of 276

and understanding disease pathogenesis.

The objectives of the research programs are to produce new research knowledge and technology to:

 prevent, reduce or eliminate losses from impaired performance, and increased deaths and condemnations;  develop more sensitive, specific and faster diagnostic tests;  develop vaccines designed for the control and, when feasible, the eradication of disease;  improve our understanding of the ecology and epidemiology of pathogens at the domestic-wild life interface; and  improve our understanding of the genetic and pathobiological basis of virulence.

This research provides government regulatory agencies and the livestock industries with improved intervention strategies against priority diseases.

(ii) Agents Microorganisms and/or Toxins:

• Overlap Select Agents Including NIAID Category B Priority Pathogens

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

The agents studied are endemic and emerging viruses and bacteria that cause diseases in livestock and poultry. The majority of the agents studied are not classified by USDA as select agents. The agents classified as select agents are pathogens that are zoonotic agents (diseases transmitted from animals to people) that pose a threat to our animal production systems, our agricultural economy, and agricultural exports.

(iii) Outdoor Studies: No research work is done outdoors with infectious organisms. Outdoor studies are conducted only for ecological purposes and monitoring of bacteria, viruses, and prions in wild life.

Page 215 of 276

Form A, Part 2 (iii)

National biological defence research and development programmes

Facilities

1. What is the name of the facility?

Southeast Poultry Research Laboratory

2. Where is it located (provide both address and geographical location)?

Agricultural Research Service, United States Department of Agriculture 934 College Station Road

Athens, Georgia 30605

3. Floor area of laboratory areas by containment level:

BL2 1138 (sqM) BL3 624 (sqM) BL4 0 (sqM) Total laboratory floor area 1762 (sqM)

4. The organizational structure of each facility.

(i) Total number of personnel 43

(ii) Division of personnel:

Military 0

Civilian 43

(iii) Division of personnel by category:

Scientists 11

Engineers 0

Technicians 19

Administrative and support staff 13

(iv) List the scientific disciplines represented in the scientific/engineering staff.

Animal Science Biochemistry Biology Biotechnology Cell Biology Page 216 of 276

Clinical Immunology Computational Biology Genetics Genomics Immunology Infectious Disease Microbiology Molecular Biology Molecular Computational Biology Pathogenesis Pathology Proteomics Public Health Statistics Vaccine Evaluation Veterinary Clinical Research Veterinary Medicine Virology

(v) Are contractor staff working in the facility? If so, provide an approximate number.

Yes Number: 3

(vi) What is (are) the source(s) of funding for the work conducted in the facility, including indication if activity is wholly or partly financed by the Ministry of Defence?

U.S. Department of Agriculture (USDA) Centers for Disease Control and Prevention (CDC) U.S. Department of Defense (DOD) - partly Non-profit Associations Private Sector Companies National Institutes of Health (NIH) Other Governmental Agencies

(vii) What are the funding levels for the following program areas: Research $ 5,800,000 Development $ 0 Test and evaluation $ 0 Total $ 5,800,000

(viii) Briefly describe the publication policy of the facility: Page 217 of 276

All scientific research data is available for publication in peer-reviewed publications after review for dual use determination. All scientists are required to have minimum of two peer- reviewed publications per year. They are encouraged to present research at scientific conferences and publish in books and proceedings.

(ix) Provide a list of publicly-available papers and reports resulting from the work during the previous 12 months. (To include authors, titles, and full references.)

Abbas, M.A., Spackman,E., Fouchier, R., Smith, D., Ahmed,Z., Siddique,N., Sarmento,L., Naeem,K., McKinley, E.T., Hameed,A., Rehmani,S., Swayne, D.E. 2011. H7 avian influenza virus vaccines protect chickens against challenge with antigenically diverse isolates. Vaccine. 29(43):7424-7429.

Cagle, C.A., To, T., Nguyen, T., Wasilenko, J.L., Adams, S.C., Cardona, C.J., Spackman, E., Suarez, D.L., Pantin Jackwood, M.J. 2011. Pekin and Muscovy ducks respond differently to vaccination with a H5N1 highly pathogenic avian influenza (HPAI) commercial inactivated virus. Vaccine. 29(38):6549-6557.

Chmielewski, R.A., Beck, J.R, Swayne, D.E. 2011. Thermal inactivation of avian influenza virus and Newcastle disease virus in a fat-free egg product. Journal of Food Protection. 74(7):1161-1168.

Costa, T., Brown, J., Howerth, E.W., Stallknecht, D.E., Swayne, D.E. 2011. Homo- and heterosubtypic low pathogenic avian influenza exposure on H5N1 highly pathogenic avian influenza virus infection in wood ducks (Aix sponsa). PLoS One. 6(1):e15987.

Deng, Q., Weng, Y., Lu, W., Demers, A., Song, M., Wang, D., Yu, Q., and Li, F. 2011. Topology and cellular localization of the small hydrophobic protein of avian metapneumovirus. Virus Research. 160:102-107.

Ecco, R., Brown, C.C., Susta, L., Cagle, C.A., Edwards, I.C., Pantin Jackwood, M.J., Miller, P.J., Afonso, C.L. 2011. In vivo transcriptional cytokine responses and association with clinical and pathological outcomes in chickens infected with different Newcastle disease virus isolates using formalin-fixed paraffin-embedded samples. Veterinary Immunology and Immunopathology. 141:221-229.

Ecco, R., Susta, L., Afonso, C.L., Miller, P.J., Brown, C.C. 2011. Neurological lesions in chickens experimentally infected with virulent Newcastle disease virus isolates. Avian Pathology. 40(2):145-152.

Estevez, C., King, D.J., Lou, M., Yu, Q. 2011. A single amino acid substitution in the hemagglutinin-neuraminidase protein of Newcastle disease virus results in increased fusion and decreased neuraminidase activities without changes in virus pathotype. Journal of Page 218 of 276

General Virology. 92:544-551.

Ewald, S.J., Kapczynski, D.R., Livant, E.J., Suarez, D.L., Ralph, J., Mcleod, S., Miller, C. 2011. Association of Mx1 Asn 631 variant alleles with enhanced resistance and altered cytokine response in chickens infected with a highly pathogenic avian influenza virus. Immunogenetics. 63(6):363-375.

Goekjian, V.H., Smith, J.T., Howell, D.L., Senne, D.A., Swayne, D.E., Stallknecht, D.D. 2011. Avian influenza viruses and avian paramyxoviruses in wintering and breeding waterfowl populations in North Carolina, USA. Journal of Wildlife Diseases. 47(1):240-245.

Hai, R., Garcia-Sastre, A., Swayne, D.E., Palese, P. 2011. A reassortment-incompetent live attenuated influenza virus vaccine for use in protection against pandemic virus strains. Journal of Virology. 85(14):6832-6843.

Kapczynski, D.R., Liljebjelke, K.A., Kulkarni, G., Hunt, H.D., Jiang, H., Petkov, D. 2011. Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza. Biomed Central (BMC) Genomics. 5(4):S13.

Mesonero, A., Suarez, D.L., Van Santen, E., Tang, D., Toro, H. 2011. Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: Vaccine potency, antibody persistence, and maternal antibody transfer. Avian Diseases. 55:285-292.

Pantin Jackwood, M.J., Strother, K.O., Zsak, L., Mundt, E., Day, J.M., Spackman, E. 2011. Molecular characterization of avian astroviruses. Archives of Virology. 156(2):235-244.

Rue, C.A., Susta, L., Edwards, I.C., Brown, C.C., Kapczynski, D.R., Suarez, D.L., King, D.J., Miller, P.J., Afonso, C.L. 2011. Virulent Newcastle disease virus elicits a strong innate immune response in chickens. Journal of General Virology. 92:931-939.

Sa E Silva, M., Mathieu, C.M., Kwon, Y., Pantin Jackwood, M.J., Swayne, D.E. 2011. Experimental infection with low and high pathogenicity H7N3 Chilean avian influenza viruses in Chiloe Wigeon (Anas sibilatrix) and Cinnamon Teal (Anas cyanoptera). Avian Diseases. 55(3):459-461.

Spatz, S.J., Schat, K.A. 2011. Comparative genomic sequence analysis of the Marek's disease vaccine strain SB-1. Virus Genes. 42:331-338.

Spatz, S.J., Smith, L.P., Baigent, S.J., Petherbridge, L., Nair, V. 2011. Genotypic characterization of two bacterial artificial chromosome clones derived from a single DNA source of the very virulent gallid herpesvirus-2 strain C12/130. Journal of General Virology. 92:1500-1507.

Susta, L., Miller, P.J., Afonso, C.L., Brown, C.C. 2011. Clinicopathological characterization in poultry of three strains of Newcastle disease viruses isolated from recent outbreaks. Page 219 of 276

Veterinary Pathology. 48(2):349-360.

Toro, H., Suarez, D.L., Tang, D.C., Van Ginkel, F.W., Breedlove, C. 2011. Avian influenza mucosal vaccination in chickens with replication-defective recombinant adenovirus vaccine. Avian Diseases. 55:43-47.

Wilcox, B.R., Knutsen, G.A., Berdeen, J., Goekjian, V., Poulson, R., Goyal, S., Sreevastan, S., Cardona, C., Berghaus, R., Swayne, D.E., Yabsley, M., Stallknecht, D. 2011. Influenza- A viruses in ducks in northwestern Minnesota: fine scale spatial and temporal variation in prevalence and subtype diversity. PLoS One. 6(9):e24010

Wang, L., Qin, Z., Pantin Jackwood, M.J., Faulkner, O.B., Suarez, D.L., Garacia, M., Lupiani, B., Reddy, S., Saif, Y., Lee, C. 2011. Development of DIVA (differentiation of infected from vaccinated animals) vaccines utilizing heterologous NA and NS1 protein strategies for the control of triple reassortant H3N2 influenza in turkeys. Vaccine. 29:7966- 7974.

Weng, Y., Lu, W., Harmon, A., Xiang, X., Deng, Q., Song, M., Wang, D., Yu, Q., Li, F. 2011. The cellular ESCRT pathway is not involved in avian metapneumovirus budding in a virus-like-particle expression system. Journal of General Virology. 92:1205-1213.

Wasilenko, J.L., Arafa, A.M., Selim, A.A., Hassan, M.K., Aly, M.M., Ali, A., Nassif, S., Elebiary, E., Balish, A., Klimov, A., Suarez, D.L., Swayne, D.E., Pantin Jackwood, M.J. 2011. Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks. Archives of Virology. 156(1):37-51.

Yu, Q., Estevez, C., Roth, J.P., Hu, H., Zsak, L. 2011. Deletion of the M2-2 gene from avian metapneumovirus subgroup C (aMPV-C) impairs virus replication and immunogenicity in turkeys. Virus Genes. 42:339-346.

5. Briefly describe the biological defence work carried out at the facility, including type(s) of microorganisms* and/or toxins studied, as well as outdoor studies of biological aerosols.

(i) Objectives: Provide scientific solutions to national and international exotic, emerging and endemic poultry viral diseases through a comprehensive research program emphasizing basic and applied research in diagnostics, prevention, and control strategies, prediction of disease outbreaks, molecular epidemiology, and understanding disease pathogenesis.

The objectives of the research program are to produce new research knowledge and technology to:

 prevent, reduce or eliminate losses from impaired performance and increased deaths and condemnations; Page 220 of 276

 develop more sensitive, specific and faster diagnostic tests;  develop vaccines designed for the control and, when feasible, the eradication of disease;  improve our understanding of the ecology and epidemiology of viruses at the wild bird-domestic poultry interface; and  improve our understanding of the genetic and pathobiological basis of virulence.

This research provides government regulatory agencies and the poultry industries with improved intervention strategies against poultry viral diseases. The Laboratory has two research units: 1) Exotic and Emerging Avian Viral Diseases Research Unit, and 2) Endemic Poultry Viral Diseases Research Unit.

(ii) Agents Microorganisms and/or Toxins:

• USDA Select Agents and Toxins • Other pathogens or toxins Including non-Select Agent, NIAID Category B and C Priority Pathogens

The agents studied are foreign and emerging viruses that cause diseases in poultry. The majority of the agents studied are classified by USDA as select agents. Some of the agents classified as select agents are pathogens that are zoonotic agents (diseases transmitted from animals to people) that pose a threat to our poultry production systems, our agricultural economy, and agricultural exports.

(iii) Outdoor Studies: No research work is done outdoors with infectious organisms. Outdoor studies are conducted only for ecological purposes and monitoring of viruses in free flying wild birds.

Page 221 of 276

Form B

BWC - Confidence Building Measure

Exchange of information on outbreaks of infectious diseases and similar occurrences caused by toxins

* Information on events reported to the World Health Organization under International Health Regulation (IHR) Public Health Emergency of International Concern (PHEIC); World Organization for Animal Health (OEI); and/or the Food and Agriculture Organization (FAO). Additional information on OIE Reportable Diseases can be found at: http://www.oie.int/wahis/public.php?page=home

United States of America

9 July 2012 Page 222 of 276

Form B (ii)

Information on outbreaks of infectious diseases and similar occurrences that seem to deviate from the normal pattern

There were four World Organization for Animal Health (OIE) immediate reports for animal disease events in 2011 (deviations from normal pattern), and three ongoing open reports from 2010. Event summaries can be found on the OIE website: http://web.oie.int/wahis/public.php?page=home

Summary of Reports

1) Contagious Equine Metritis (OIE Immediate Report July 27, 2011 - Ongoing). Contagious equine metritis is an inflammation of the endometrium of mares caused by Taylorella equigenitalis, which usually results in temporary infertility. It is a nonsystemic infection, the effects of which are restricted to the reproductive tract of the mare. Taylorella equigenitalis is most frequently transmitted by sexual contact with carrier stallions, which are always asymptomatic.

On July 21, 2011, a 4-year-old Arabian stallion in Arizona was confirmed positive for Taylorella equigenitalis, the bacterium that causes contagious equine metritis (CEM), during routine semen exportation screening. There is currently no known relationship between this CEM positive stallion and any other horses associated with previous U.S. cases of CEM. The epidemiological investigation identified 17 stallions and 13 mares that were potentially exposed to the infected stallion. All identified exposed animals are/were quarantined until determined CEM-negative and completed the required testing and treatment protocols. No additional positive animals were identified. The epidemiological investigation of this event continues as of the time of writing.

2) White Spot Syndrome Virus (OIE Immediate Report October 24, 2011 - Ongoing). White spot syndrome virus (WSSV) is a Whispovirus of the family Nimaviridae that infects a wide range of aquatic crustaceans. Disease is predominately seen in shrimp and may include color change, the appearance of white spots, lethargy, and high mortality.

On October 13, 2011, the National Veterinary Services Laboratories (NVSL) confirmed white spot syndrome virus (WSSV) on a white legged meat shrimp farm on Kauai, Hawaii. A small increase in mortality was noticed in a few of the ponds at the meat production facility. The facility was placed under quarantine, all ponds were covered with nets, and affected ponds are in the process of harvest, cleaning and disinfection. Restocked shrimp will be tested for WSSV to verify that proper cleaning and disinfection occurred.

3) Low Pathogenic Notifiable Avian Influenza (LPNAI) - Two OIE Immediate Reports in 2011. H5 and H7 avian influenza in its low pathogenic form in poultry is a notifiable disease as per Chapter 10.4 on avian influenza of the OIE Terrestrial Animal Health Code (2008): http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_1.10.4.htm Page 223 of 276

 Polk County, Missouri (OIE Immediate Report March 29, 2011 - Resolved May 26, 2011)

Routine preslaughter surveillance testing performed as part of the National Poultry Improvement Plan (NPIP) detected H7N3 LPNAI in Polk County, Missouri. The index premises was a commercial turkey operation consisting of 14,000 affected 19-week-old turkeys in two separate houses, and an additional 15,000 exposed 5-week-old turkeys on the premises. No clinical signs of disease or increased mortality were noted. The Missouri H5/H7 Initial State Response and Containment plan was implemented, enhanced surveillance was conducted, and the market weight birds were sent to slaughter, while the 5-week-old turkeys were depopulated as a precautionary measure.

 Wright County, Minnesota (OIE Immediate Report June 29, 2011 - Resolved August 1, 2011)

On June 29, 2011, the National Veterinary Services Laboratories (NVSL) confirmed H7N9 LPNAI in a commercial turkey flock located in Minnesota. The birds in the flock showed no signs of clinical illness or increased mortality; initial detection of infection was identified through routine pre-slaughter surveillance testing. Enhanced surveillance was conducted as outlined in the Minnesota H5/N7 LPNAI Initial State Response and Containment Plan. Due to a high temperatures in the area in July, with a heat index value of well above 100° Fahrenheit (37.8 Celsius), the turkey flock suffered a heat related death loss of 2,500 turkeys. Samples were submitted to the University of Minnesota Veterinary Diagnostic Lab, and gross findings were consistent with death due to heat stress. The death loss was not related to avian influenza. The remaining birds were depopulated via controlled marketing.

4) Equine piroplasmosis - Three OIE Ongoing Reports in 2011. Equine piroplasmosis is a tick- borne protozoal disease of horses, mules, donkeys, and zebra. The aetiological agents are blood parasites named Theileria equi and Babesia caballi.

National Outbreak (2 ongoing OIE reports: T. equi and B. caballi)

Testing for interstate movement and movement to equine events in response to the recent equine piroplasmosis (EP) outbreaks continues in many States. As of January 1, 2012, 184 T. equi and 6 Babesia caballi-positive horses were detected in 21 States: AL, CA, CO, FL, GA, IL, IN, IA, KY, LA, MA, MI, MN, MS, NM, NC, OH, OK, SC, TN, and TX. Unlike the South Texas outbreak, transmission of the organism likely resulted from management practices (use of shared needles or substances between horses) rather than by a tick vector. Additionally, some of the EP- positive horses detected were imported prior to August 2005 when the official import test became the competitive enzyme-linked assay (cELISA). These imported horses are considered to have acquired their infections prior to arrival in the United States. Individual State movement testing for equine piroplasmosis continues in 2012.

South Texas Outbreak (Ongoing OIE report) Page 224 of 276

Equine piroplasmosis (Theileria equi) was identified in South Texas on October 19, 2009. During the outbreak investigation, 2,500 horses were tested and 413 T. equi-positive horses were detected. T. equi-positive horses were identified in 17 States: AL, CA, CO, FL, GA, IN, LA, MN, MO, NM, NC, NJ, OK, TX, TN, UT, WI. The T. equi-positive horses were either moved back to the index ranch in Texas to be managed under long-term quarantine, euthanized, or enrolled in research programs. Approximately 220 quarantined horses are undergoing treatment for research purposes. The results of the epidemiological investigation indicate that infection was likely present on the index ranch prior to 1990. Extensive tick studies on the index premises found one known experimental tick vector for T. equi, Dermacentor variablis, and determined via testing that a second tick species, Amblyomma cajennense, was also capable of transmitting T. equi. The epidemiological investigation has concluded for this outbreak.

5) Equine Herpes Virus 1 Outbreak (disease deviating from normal pattern; not an OIE reportable event) http://www.aphis.usda.gov/vs/nahss/equine/ehv/

Equine Herpes Virus (EHV-1) infection in horses can cause respiratory disease, abortion in mares, neonatal foal death, and/or neurologic disease. The neurologic form of EHV-1 is called Equine Herpes Virus Myeloencephalopathy (EHM). The virus can spread through the air, contaminated equipment, clothing and hands. EHV-1 is endemic to the United States and is usually handled by the States involved; USDA becomes involved in cases involving multiple States or movement of horses across State lines.

Several horses that competed in the National Cutting Horse Association Western National Championship in Ogden, Utah, on April 29-May 8, 2011, were diagnosed with EHV-1. Following that event, reports were received about affected horses from multiple States and Western Canada, with several fatalities. A total of 90 confirmed EHV-1 or EHM cases were reported in 10 States (AZ, CA, CO, ID, NM, NV, OK, OR, UT, and WA).

Page 225 of 276

Form B (ii)

Information on outbreaks of infectious diseases and similar occurrences that seem to deviate from the normal pattern

On October 26, 2011, the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) confirmed the first U.S. detection of a fungal pathogen, Cylindrocladium pseudonaviculatum (boxwood blight) in Surry County, North Carolina. Subsequent detections were confirmed in Middlesex County, Connecticut, and Carroll County, Virginia.

In response to these confirmations, APHIS is working closely with the affected state departments of agriculture to survey and delimit the areas for additional detections, as well as obtain trace back and trace forward information. APHIS also initiated a targeted detection survey to determine if this pathogen is present in other eastern states.

Boxwood blight can impact the appearance and aesthetic appeal of its host plant Buxaceae: Buxus colchica, B. microphylla (littleleaf boxwood), B. microphylla var. japonica (Japanese boxwood), B. sempervirens (common boxwood), B. sempervirens Suffruticosa (common boxwood, dwarf cultivar), B. sinica (Korean boxwood), and B. sinica var. insularis (Korean boxwood). The pathogen is known to occur in Europe, including the countries of Belgium, Croatia, France, Georgia, Germany, Ireland, Italy, the Netherlands, Slovenia, Spain, Switzerland, and the United Kingdom as well as in Oceania in New Zealand.

Under the International Plant Protection Convention standards, Cylindrocladium pseudonaviculatum is considered to be a pest that is present, only in some areas.

This report was created based on an APHIS State Plant Regulatory Official (SPRO) letter #DA- 2011-67, dated December 05, 2011. Page 226 of 276

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern

1. Time of cognizance of the outbreak Mid June 2011

2. Location and approximate area affected San Luis Rio Colorado, Sonora, Mexico/Yuma County, Arizona, USA

3. Type of disease/intoxication Guillain-Barré syndrome (GBS) associated with Campylobacter infection.

4. Suspected source of disease/intoxication Municipal water in San Luis Rio Colorado

5. Possible causative agent(s) Campylobacter jejuni

6. Main characteristics of systems Neurologic - acute symmetric polyneuropathy, predominant motor dysfunction.

7. Detailed symptoms, when applicable - neurological/behavioural - acute flaccid paralysis, specifically acute motor axonal neuropathy and Fisher Syndrome, Brighton level 3 or higher - intestinal - antecedent fever,

diarrhea and abdominal cramps

8. Deviation(s) from the normal pattern as regards GBS rarely occurs in time-space clusters, first known cluster in North America

9. Approximate number of primary cases 26 cases of GBS meeting Brighton criteria

10. Approximate number of total cases 31 total cases of AFP

11. Number of deaths 1

12. Development of the outbreak The first cases of GBS were detected locally in early to mid May and new cases continued through early July. Most cases (81%) had a recent history of diarrhea and, several lines of evidence indicated that most or all of the cases were due to Campylobacter infection, a frequently identified antecedent of GBS. A community wide diarrhea outbreak was noted in Page 227 of 276

San Luis Rio Colorado starting around the beginning of May. Yuma County, Arizona, detected an increase in Campylobacter reports starting in early May. Eighteen of the GBS cases resided in Mexico and eight in the US. A binational investigation commenced in late June leading to a case control study to evaluate food, water, animal and environmental exposures associated with illness. Results suggest that contaminated water which may have been ingested in small quantities through contact with irrigation or municipal water was the source of the outbreak of C. jejuni infection and GBS.

13. Measures taken The likely source of the outbreak, the municipal and irrigation water supply, was not determined until after the outbreak was over. However, shock chlorination of the San Luis Rio Colorado municipal water system that was performed on June 20 because of the detection of low chorination levels may have played an important role in ending the outbreak. Measures were taken to heighten surveillance for neurologic and gastrointestinal

illness, and general recommendations were made to the public to regarding foodborne disease prevention. Consultations between San Luis Rio Colorado, Sonora, and Yuma, Arizona municipal water authorities and CDC took place and plans for ongoing communication were put in place.

Page 228 of 276

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern

1. Time of cognizance of the outbreak Outbreak occurred during August 2011-October 2011.

2. Location and approximate area affected A total of 43 individuals infected with the outbreak strain of Salmonella Enteritidis were reported from 5 states. The number of ill persons identified in each state with the outbreak strain was as follows: Maryland (1), New Jersey (2), New York (28), Pennsylvania (8), and Virginia (4).

3. Type of disease/intoxication Salmonellosis (gastrointestinal illness from Salmonella infection)

4. Suspected source of disease/intoxication Consumption of contaminated pine nuts.

5. Possible causative agent(s) Salmonella enterica serotype Enteritidis

6. Main characteristics of systems Intestinal illness

7. Detailed symptoms, when applicable intestinal: Most persons infected with Salmonella bacteria develop diarrhea, fever, and abdominal cramps 12 to 72 hours after infection. The illness usually lasts four to seven days, and most persons recover without treatment. However, in some persons, the diarrhea may be so severe that the patient needs to be hospitalized. Salmonella infection may spread from the

intestines to the bloodstream and then to other body sites and can cause death unless the person is treated promptly with antibiotics. Older adults, infants, and those with impaired immune systems are more likely to have a severe illness from Salmonella infection.

8. Deviation(s) from the normal pattern as regards Place of occurrence: Increased number of isolates uploaded in Northeastern states presence of unusual vectors: First Salmonella outbreak in the United States linked to pine nuts

9. Approximate number of primary cases 43

10. Approximate number of total cases 43

11. Number of deaths Page 229 of 276

12. Development of the outbreak CDC collaborated with public health and agriculture officials in New York and other states and the U.S. Food and Drug Administration (FDA) to investigate a multistate outbreak of Salmonella Enteritidis infections linked to Turkish pine nuts purchased from bulk bins at Wegmans grocery stores. Representatives from Wegmans cooperated with public health officials throughout the investigation. Public health investigators used DNA "fingerprints" of Salmonella bacteria obtained through diagnostic testing with pulsed-field gel electrophoresis, or PFGE, to identify cases of illness that may have been part of this outbreak. They used data from PulseNet, the national subtyping network made up of state and local public health laboratories and federal food regulatory laboratories that performs molecular surveillance of foodborne infections. Among 43 persons for whom information was available, illnesses began on or after August 20, 2011. Ill persons ranged in age from <1 to 94 years, and the median age was 43 years old. Sixty percent of patients were female. Two patients were hospitalized. No deaths were reported. Epidemiologic and laboratory investigations conducted by officials in local, state, and federal public health, agriculture, and regulatory agencies linked this outbreak to eating Turkish pine nuts sold in bulk bins at Wegmans grocery stores. Some Turkish pine nuts were consumed as an ingredient in prepared foods, such as Caprese salad or asparagus with pine nuts, sold at Wegmans stores. These pine nuts were imported from Turkey. Among 40 ill persons for whom information was available, 28 (70%) reported consuming Turkish pine nuts or products containing these pine nuts in the week before their illness began. Early in the investigation, shopper card information was collected and used to identify which specific products to suspect as sources of illness. Ill persons gave permission for public health officials to retrieve shopper card purchase information. A review of shopper card records identified that ill persons had purchased the same type of Turkish pine nuts from bulk bins at different locations of Wegmans grocery stores before becoming ill. Laboratory testing conducted by public health laboratories in several states identified the outbreak strain of Salmonella Enteritidis from 14 samples of Turkish pine nuts or homemade pesto containing Turkish pine nuts purchased from bulk bins at Wegmans stores and collected from ill persons' homes or from retail samples of Turkish pine nuts collected from Wegmans stores. In addition, laboratory testing conducted by FDA isolated the outbreak strain of Salmonella Enteritidis from Turkish pine nuts collected by FDA from a warehouse used by Sunrise Commodities and from a warehouse used by a customer of Sunrise Commodities.

13. Measures taken CDC posted updates about the outbreak investigation on the CDC website on 10/26/2011, 11/3/2011, and 11/17/2011 (available at: http://www.cdc.gov/salmonella/pinenuts- enteriditis/index.html). On October 26, 2011 , Wegmans Food Markets, Inc. recalled approximately 5,000 lbs of Turkish Pine Nuts sold in the Bulk Foods department of most Wegmans stores in New York, Pennsylvania, New Jersey, Virginia, and Maryland between July 1 and October 18, 2011. On November 4, 2011 , Badia Spices, Inc. recalled approximately 3,800 lbs. of pine nuts. Badia Spices, Inc. repacked bulk pine nuts which were imported from Turkey and subsequently recalled by Sunrise Commodities of Page 230 of 276

Englewood Cliffs, N.J. These pine nuts were sold in retail stores in Florida, New York, Pennsylvania, Maryland, and New Jersey between June and October 2011. On November 9, 2011 , FDA confirmed the presence of Salmonella on tested Turkish pine nuts distributed by Sunrise Commodities. The company voluntarily recalled four lots of the bulk Turkish pine nuts, totaling more than 21,000 pounds. Each lot was packed in 22-pound boxes. Sunrise Commodities distributed the Turkish pine nuts in bulk to various food vendors in Florida, New Jersey, New York, and Canada. Sunrise Commodities issued a recall notification to its customers dated November 3, 2011, alerting them of the test results and of the epidemiologic investigation and asking them to notify their subsequent customers of the recall. On November 30, 2011, FDA placed two foreign suppliers of Turkish Pine Nuts to Sunrise Commodities on Import Alert (#99-19).

Page 231 of 276

Form B

Information on outbreaks of infectious diseases and similar occurrences, that seem to deviate from the normal pattern

1. Time of cognizance of the outbreak Outbreak detected by PulseNet on April 11, 2011.

2. Location and approximate area affected A total of 106 individuals infected with the outbreak strain of Salmonella Agona were reported from 25 states between January 1 and August 25, 2011. The number of ill persons identified in each state with the outbreak strain was as follows: Arkansas (1), Arizona (4), California (8), Colorado (1), Georgia (8), Illinois (18), Indiana (1), Kentucky (1), Louisiana

(2), Massachusetts (1), Minnesota (3), Missouri (3), Nebraska (2), Nevada (1), New Jersey (1), New Mexico (3), New York (9), Ohio (1), Oklahoma (1), Pennsylvania (2), Tennessee (1), Texas (25), Virginia (2), Washington (5), and Wisconsin (2).

3. Type of disease/intoxication Salmonellosis (gastrointestinal illness from Salmonella infection).

4. Suspected source of disease/intoxication Consumption of contaminated fresh papayas imported from Mexico.

5. Possible causative agent(s) Salmonella enterica serotype Agona

6. Main characteristics of systems Gastrointestinal illness

7. Detailed symptoms, when applicable Intestinal: Most persons infected with Salmonella bacteria develop diarrhea, fever, and abdominal cramps 12 to 72 hours after infection. The illness usually lasts four to seven days, and most persons recover without treatment. However, in some persons, the diarrhea may be so severe that the patient needs to be hospitalized. Salmonella infection may spread from the

8. Deviation(s) from the normal pattern as regards Type: The strain of Salmonella Agona associated with this outbreak is composed of four closely related PFGE patterns that had been rarely identified before in PulseNet. Three of these four PFGE patterns were first identified beginning in 2010. A total of 119 cases from 14 states were reported between May 28, 2010, and September 10, 2010. Distribution of age, sex, ethnicity, and state of residence among ill persons was similar to the distribution seen in the current outbreak. Despite an intensive investigation during the summer of 2010 by local, Page 232 of 276

state, and federal public health agencies that focused on fresh fruit, including papaya, the source of the 2010 outbreak was not determined. Presence of unusual vectors: First Salmonella outbreak in the United States linked to papayas was confirmed in 2011.

9. Approximate number of primary cases 106

10. Approximate number of total cases 106

11. Number of deaths None

12. Development of the outbreak CDC and the U.S. Food and Drug Administration (FDA) collaborated with public health officials in Texas, Illinois, Georgia, and other states to investigate a multistate outbreak of Salmonella Agona infections linked to whole, fresh papayas imported from Mexico. Public health investigators used DNA "fingerprints" of Salmonella bacteria obtained through diagnostic testing with pulsed-field gel electrophoresis, or PFGE, to identify cases of illness that were part of this outbreak. They used data from PulseNet, the national subtyping network made up of state and local public health laboratories and federal food regulatory laboratories that performs molecular surveillance of foodborne infections. Among persons for whom information is available, illnesses began on or after January 17, 2011. Ill persons ranged in age from less than 1 year old to 91 years old, and the median age was 21 years old. Thirty-nine percent of patients were younger than 5 years old. Fifty-six percent were female. Eleven persons reported travel to Mexico in the week before they became ill. Ten patients were hospitalized. No deaths were reported. Epidemiologic, traceback, and laboratory investigations conducted by officials in many local, state, and federal public health, agriculture, and regulatory agencies linked this outbreak to eating fresh, whole papayas imported from Mexico by Agromod Produce, Inc. of McAllen, Texas. Among 56 ill persons for whom information is available, 57% reported consuming papayas in the week before illness onset. This was significantly different compared with results from a survey of healthy persons in which 11% of persons of Hispanic/Latino ethnicity and 3% of non- Hispanic/Latino ethnicity reported consuming papaya in the 7 days before they were interviewed. Product information such as date and location of purchase of papayas was collected from ill persons and used by local, state, and federal public health, agriculture, and regulatory agencies to conduct traceback investigations. Agromod Produce, Inc. was identified as a common supplier of papayas purchased by ill persons. Sampling of papayas by FDA as part of the outbreak investigation identified two samples with Salmonella Agona that were indistinguishable by PFGE from the outbreak strain. One sample was collected at Agromod Produce, Inc. in McAllen, Texas and the other was collected at the U.S.-Mexico border from a shipment destined for Agromod Produce, Inc. These papayas had been imported from Mexico. The shipments from which Salmonella was isolated were not distributed in the United States. Page 233 of 276

13. Measures taken CDC posted updates about the outbreak investigation on the CDC website on 7/25/2011, 7/26/2011, 8/29/2011 (available at http://www.cdc.gov/salmonella/agona- papayas/index.html) On July 23, 2011, Agromod Produce, Inc. voluntarily recalled fresh, whole papayas because they have the potential to be contaminated with Salmonella. The recall includes all Blondie, Yaya, MaÃ±anita, and Tastylicious Brand papayas sold prior to July 23, 2011. These fresh, whole papayas were imported from Mexico and distributed nationwide in the United States and to Canada through retail stores and wholesalers. From

May 12, 2011, to August 18, 2011, FDA analysis found a 15.6% Salmonella contamination rate. The positive samples were from 28 different firms and include nearly all the major papaya producing regions in Mexico. Under an FDA Import Alert issued on August 25, 2011, papayas from each source in Mexico may be denied admission into the United States unless the importer shows they are not contaminated with Salmonella. The full text of this alert is available at: http://www.accessdata.fda.gov/CMS_IA/importalert_721.html .

Page 234 of 276

Form C

BWC - Confidence Building Measure

Encouragement of Publication of Results and Promotion of Use of Knowledge

United States of America

9 July 2012 Page 235 of 276

FORM C

Encouragement of Publication of Results and Promotion of Use of Knowledge

U.S. Department of Health and Human Services (HHS) Open Government Plan and the HHS Strategic Plan 2010-2015

The U.S. Department of Health and Human Services (HHS) Open Government Plan represents the official response of the U.S. Department of Health and Human Services (HHS) to the White House's Open Government Directive, issued on December 8, 2009. The plan embraces the idea of working proactively and energetically to advance a culture of Open Government at HHS.

HHS believes that transparency and data sharing are of fundamental importance to its ability to achieve its strategic goals of advancing the health and well-being of the United States. HHS's vast stores of data are a remarkable resource which can be utilized to help citizens understand what HHS does and hold it accountable, help the public hold the private sector accountable, increase awareness of health and human services issues, generate insights into how to improve health and well-being, spark public and private sector innovation and action, and provide the basis for new products and services.

This plan also seeks to take Open Government to the next level by expanding opportunities for public participation in HHS activities and for collaboration across HHS and with the world outside HHS - especially via the use of new information and communications technologies.

The HHS Open Government Plan is available online at: http://www.hhs.gov/open/plan/opengovernmentplan/openplanversion1_1.pdf , and HHS's Open Government Progress Report, highlighting some of the most important developments in HHS's Open Government Initiative, including Transparency and Data Sharing, is available at: http://www.hhs.gov/open/plan/june2011progressreport/index.html.

The HHS Strategic Plan 2010-2015 describes HHS' work to address complex, multifaceted, and ever-evolving health and human service issues. Goal 4 of this plan is to Increase Efficiency, Transparency, and Accountability of HHS Programs.

HHS embraces the power of Open Government, recognizing that with openness comes responsibility and accountability for results. Through Open Government, HHS is promoting transparency, participation, and collaboration-vital enablers of success in the HHS mission to improve the health and well-being of all Americans. HHS's Open Government efforts will break new ground in enabling the public to give feedback to HHS programs. HHS can help stakeholders contribute knowledge and experience to help it do jobs better, and HHS can support new kinds of collaborative teamwork that will deliver better results for our citizens. HHS will move forward toward new strategies, new tools, and a new culture of public participation and collaboration in its affairs.

The HHS Strategic Plan is available as a web document at: http://www.hhs.gov/secretary/about/priorities/priorities.html Page 236 of 276

The Policy on Releasing and Sharing Data at the US Department of Health and Human Services (HHS) and its Components

There are a number of federally mandated regulations and clearance functions that affect the research and practice of HHS (for a list of HHS agencies and offices, please see: http://www.hhs.gov/about ). They apply to all HHS employees, contractors, and awardees conducting data collection activities, whether the activities are for research or public health practice or occur in domestic or global settings. Examples include the HHS/FDA regulations for the protection of human research participants and compliance with the Federal Animal Welfare Act (AWA) as well as the Public Health Service Policy on Humane Care and Use of Laboratory Animals. In addition, the Paperwork Reduction Act (PRA), the Privacy Act, the Public Health Service Act (PHSA), the E-Government Act of 2002, the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, and the Family Educational Rights and Privacy Act (FERPA) all include legislation or regulations that affect the research and public health practice.

HHS believes that public health and scientific advancement are best served when data are released to, or shared with, other public health agencies, academic researchers, and appropriate private researchers in an open, timely, and appropriate way. While recognizing the value of releasing data quickly and widely, HHS also considers the need to maintain high standards for data quality, the need for procedures that ensure that the privacy of individuals who provide personal information is not jeopardized, and the need to protect information relevant to national security, criminal investigations, or misconduct inquiries and investigations. The goal is to have a policy on data release and sharing that balances the desire to disseminate data as broadly as possible with the need to maintain high standards and protect sensitive information.

Within this framework, specific HHS agencies and offices may have their own guidance for releasing and sharing data. The Centers for Disease Control (CDC) Policy on Releasing and Sharing Data is available online at: http://www.cdc.gov/maso/Policy/ReleasingData.pdf, and the National Institutes of Health (NIH) data Sharing Policy and Implementation Guide is available online at: http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm.

The Journal Emerging Infectious Diseases

This journal is published by the Centers for Disease Control and Prevention (CDC), and is ranked 3rd out of 58 infectious disease journals. Emerging Infectious Diseases receives more than 1,800 manuscripts each year (most unsolicited, some invited) from authors around the world. It has 17,000 subscribers to the print version in more than 100 countries and 33,000 subscribers to the electronic table of contents. The journal site receives hundreds of thousands of hits per month (CDC Web Statistics, http://wwwnc.cdc.gov/eid/pages/about.htm)

Emerging Infectious Diseases is available online at: http://wwwnc.cdc.gov/eid/

The Morbidity and Mortality Weekly Report (MMWR) and Surveillance Summaries from the Centers for Disease Control and Prevention (CDC) Page 237 of 276

The MMWR series is often called "the voice of CDC." It is the agency's primary vehicle for scientific publication of timely, reliable, authoritative, accurate, objective, and useful public health information and recommendations. MMWR readership predominantly consists of physicians, nurses, public health practitioners, epidemiologists and other scientists, researchers, educators, and laboratorians. The data in the weekly MMWR are provisional, based on weekly reports to CDC by state health departments.

The Surveillance Summaries provide a means for CDC programs to disseminate surveillance findings, permitting detailed interpretation of trends and patterns based on those findings.

The MMWR series is available online at: http://www.cdc.gov/mmwr/publications/index.html

The CDC Surveillance Summaries are available online at: http://www.cdc.gov/mmwr/mmwr_ss/ss_cvol.html

The Excellence in Science Committee (EISC) at the Centers for Disease Control and Prevention (CDC)

The EISC promotes the CDC's scientific infrastructure and facilitates communication and collaboration that enhance scientific areas and activities needed for state-of-the-art conduct of science to foster, support, and protect an environment for the promotion of scientific integrity, quality assurance, and the rapid dissemination of scientific innovations, technology, and information with the ultimate goal of improving public health.

More information about the EISC is available online at: http://www.cdc.gov/od/science/excellence/

The Center for Disease Control and Prevention (CDC) Clearance Policies

The Office of the Associate Director for Science (OADS) at the Center for Disease Control and Prevention (CDC) provides service and support to the CDC scientists as they work to protect people's health and improve the quality of their lives. OADS' focus is on strengthening the quality and integrity of CDC's science and is home to the Office of Science Quality and the Office of Scientific Integrity. Furthermore, by fostering innovative and successful scientific collaborations and partnerships OADS is also working towards enhancing the relevance of CDC's science and its health impact.

OADS is also home to the Office of Science Quality (OSQ), which is responsible for advancing the quality of CDC's science and championing the translation of research through the development of science policies and best practices (e.g., authorship, scientific clearance, peer review, and extramural research policies); and the Office of Scientific Integrity, which ensures that CDC science and research activities comply with various federal laws, regulations, and policies; coordinates the agency's 301(d) and 308(d) confidentiality protections; ensures leadership in public health ethics; and provides trainings to promote a well-educated and ethical domestic and international workforce at CDC. Page 238 of 276

Publication is encouraged and managed by editorial and clearance policies conducted at all levels of the Agency.

CDC Policy on oversight and clearance of dual use research of concern is available online at: http://aops-mas-iis.cdc.gov/Policy/Doc/policy516.pdf

Public Health Image Library

The Centers for Disease Control and Prevention (CDC) created the Public Health Image Library (PHIL), recognizing that much of the information critical to the communication of public health messages is pictorial rather than text-based. The PHIL offers an organized, universal electronic gateway to CDC's pictures. Public health professionals, the media, laboratory scientists, educators, students, and the worldwide public are welcome to use this material for reference, teaching, presentation, and public health messages. The content is organized into hierarchical categories of people, places, and science, and is presented as single images, image sets, and multimedia files.

The PHIL is available online at: http://phil.cdc.gov/

The US Food and Drug Administration (FDA) Publications

The FDA encourages its scientists to publish their findings in peer-reviewed science journals, books, and related articles.

A list of publications (per calendar year) covering the areas of animal health, analytical methods, and animal and food microbiology is available online at: http://www.fda.gov/AnimalVeterinary/ScienceResearch/ResearchAreas/ucm107413.htm

A list of publications on drug development and drug interactions is available online at: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio nsLabeling/ucm091806.htm

A list of publications from the FDA's National Center for Toxicological Research (NCTR) is available online at: http://www.fda.gov/AboutFDA/CentersOffices/OC/OfficeofScientificandMedicalPrograms/NCT R/WhatWeDo/NCTRPublications/ucm077352.htm

The US Food and Drug Administration (FDA) Office of Science and Engineering Laboratories (OSEL) Annual Report

The OSEL Annual Report provides current information about the Office's organization and intramural science activities; provides a summary of the Office's direct laboratory support for pre-market review and compliance cases; and provides a bibliography of scientific publications, presentations, and research seminars for the fiscal year. Page 239 of 276

Annual reports are available online at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CD RHReports/ucm109778.htm

The National Institutes of Health (NIH) Public Access Policy

The NIH Public Access Policy ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the National Library of Medicine's digital archive PubMed Central (http://www.ncbi.nlm.nih.gov/pmc/) upon acceptance for publication. To help advance science and improve human health, the Policy requires that these papers are accessible to the public on PubMed Central no later than 12 months after publication.

The NIH Public Access Policy is available online at: http://publicaccess.nih.gov/policy.htm

The National Institutes of Health (NIH) Review Mechanism for Dual Use Research Manuscripts

The NIH has established a review mechanism for manuscripts which may involve dual use research of concern.

The Publication and Abstract Clearance Form is available online at: http://www1.od.nih.gov/oir/sourcebook/oversight/pub-clear-form.htm

The Dual Use Questionnaire is available online at: http://sourcebook.od.nih.gov/oversight/Dual%20Use%20Questionnaire-4-2010.pdf

The National Institutes of Health (NIH) Instruction in the Responsible Conduct of Research

The NIH requires that all trainees, fellows, participants, and scholars receiving support through any NIH training, career development award (individual or institutional), research education grant, and dissertation research grant must receive instruction in responsible conduct of research. Responsible conduct of research is defined as the practice of scientific investigation with integrity. It involves the awareness and application of established professional norms and ethical principles in the performance of all activities related to scientific research.

The NIH Policy is available online at: http://grants1.nih.gov/grants/guide/notice-files/NOT-OD- 10-019.html

NIH materials for Research Conduct and Ethics Instruction, including case studies for the 2012 theme (Mentoring) are available online at: http://sourcebook.od.nih.gov/resethicscases/cases- toc.htm Page 240 of 276

Form E

BWC - Confidence Building Measure

Declaration of legislation, regulations and other measures

United States of America

9 July 2012 Page 241 of 276

Form E

Declaration of legislation, regulations and other measures

Amended Since Last Legislation Regulations Other year

Development, production, stockpiling, acquisition or retention of microbial or other biological agents, YES YES YES YES or toxins, weapons, equipment and means of delivery specified in Article I Import of Micro-Organisms* and Toxins. YES YES YES YES Export of Micro-Organisms* and Toxins. YES YES NO YES Biosafety11 and biosecurity12 YES YES YES YES

FBI Biosecurity Outreach to Academic Science Community During 2011, the FBI conducted ten biosecurity outreach events to research institutions across the United States. These outreach events provided an environment where law enforcement and the academic science communities (research students, professors/researchers, biosafety officers, etc.) could engage in mutually beneficial dialogue. During these events, the FBI aimed to: 1) improve situational awareness of biosecurity threats, and 2) foster a mechanism for academia to report suspicious activities. The FBI works to enhance the science community's awareness of threats and vulnerabilities, both internal and external, as scientists can be exploited because of their expertise and access to biological material/technologies. Additionally, the FBI educates the science community of the FBI's roles and responsibilities in the biosecurity arena and provides resources that can be used to mitigate suspicious activities observed, such as contacting their local FBI WMD Coordinator, the point of contact in every FBI Field Office across the U.S. The WMD Coordinator can in turn offer expertise and resources from Federal, State, and local agencies for mitigation. Law enforcement and science collaboration also fosters better understanding of what type of biosecurity policies are needed to suit both FBI and science research needs. This understanding allows the FBI to advise policymakers on policy that improves security without impeding research.

FBI Biosecurity Outreach to Synthetic Biology Sector During 2011, the FBI conducted its annual Synthetic Biology Workshop, which aims to take a proactive approach in mitigating current and potential future risks posed by the exploitation and misuse of emerging scientific fields such as synthetic biology. The FBI has fostered mutually beneficial partnerships with several prominent synthetic biology companies. These partnerships provide the synthetic biology industry enhanced awareness of biosecurity threats and resources Page 242 of 276 they can use to mitigate suspicious customers/sequence orders. By fostering a proactive relationship with the synthetic biology industry, the FBI gains greater insight into obstacles and needs of the synthetic biology industry, which can lead to more effective guidance, policy, regulations, and statues. The synthetic biology industry, in turn, has a reporting mechanism in place with local FBI WMD Coordinators, should they receive suspicious requests and is able to provide the FBI insight regarding the field's current status and areas of advancement. In addition, the FBI conducted biosecurity engagement with the International Genetically Engineered Machine Competition, which is the largest, annual synthetic biology meeting of undergraduate students worldwide. FBI has engaged with the organizers and competitors since 2009 and was able to institute a biosecurity judging criterion, which encourages and obligates the competitors to assess and address potential biosecurity issues with their projects.

FBI Biosecurity Outreach to the Amateur Biology Community During 2011, the FBI conducted one biosecurity outreach event with the amateur biology community in the United States. Over the past decade, the FBI has witnessed the rapid growth of amateur biology communities. These groups believe that opportunities to develop advances in science and biotechnology, just like the early computer revolution, should be made available outside of traditional academic and industrial settings, i.e. garage or community laboratory. The FBI has developed partnerships with the amateur biology community in order to garner their assistance in preventing, detecting, and responding to incidents of misuse, particularly for nefarious purposes. The FBI efforts focus primarily on outreach and awareness of potential threats. This outreach includes attendance at amateur biology conferences and regional meetings, FBI-sponsored national workshops, assistance in the development of a safety and security framework, and dissemination of education materials. By hosting an outreach workshop, the FBI continued to foster the development of a culture of responsibility and opening lines of communication between members of the amateur biology community and their respective local FBI WMD Coordinator to facilitate the reporting of suspicious activity.

FBI Enforcement of Legislation To implement Article I of the BWC, the United States established the Biological Weapons Antiterrorism (BWAT) Act, which establishes BWC violations as a federal crime, consistent with U.S. Article IV commitments. The BWAT Act was codified in the U.S. federal criminal code (Title 18 of the United States Code, Section 175(a) and (b); also referred to as 18 USC 175). As a result, individual(s) in the United States can be charged with a federal crime if they use a biological agent, toxin, or delivery system as a weapon, or are in possession of any biological agent without justifiable research or peaceful purpose. It is also a crime to knowingly possess a Select Agent or toxin, regardless of intent, if the individual does not have legitimate access (registered with the U.S. Federal Select Agent Program) and purpose. In 2011, the FBI responded to several incidents that involved biological material and led investigations that resulted in the prosecutions for the violation of 18 USC 175.

FBI Security Risk Assessments (SRAs) - 4,015 SRAs Completed in 2011 The FBI conducts Security Risk Assessments (SRAs), a requirement of the U.S. Federal Select Agent Program (SAP), on all entities and personnel in the United States requesting possession, use, or transfer of biological select agents and toxins (BSAT). Using various biographical and biometric databases, the FBI determines if a candidate meets the criteria of a "restricted person" Page 243 of 276 based upon a list of prohibitors found under 18 U.S. Code 175b (derived from the USA PATRIOT Act and the Public Health Security and Bioterrorism Preparedness and Response Act). In 2011, 4,015 SRAs were processed by the FBI (Criminal Justice Information Services Division, Biosecurity Risk Assessment Group). Of the 4,015 individual SRAs processed, 27 BSAT access candidates were determined to meet the criteria of a "restricted person." The FBI's adjudication is provided to the Department of Health and Human Services or the Department of Agriculture, who decide whether to grant or deny the requesting entity or individual access to BSAT. In response to a recommendation from the Federal Experts Security Advisory Panel, the SAP increased the frequency of conducting SRAs from five years to three years for both new and renewing candidates beginning on June 1, 2011.

FBI/CDC Joint Criminal and Epidemiological Investigation Training During 2011, the FBI conducted five Joint Criminal and Epidemiological Investigations training courses across the United States. These 2-day courses focused on improving local response plans and information-sharing protocols, educating participants on the benefits of the joint investigation and interview models and fostering relationships between the law enforcement and public health communities to rapidly assess whether the origin of an unusual outbreak was natural or intentional. Through this effort, law enforcement and public health gain familiarity with criminal and epidemiological investigations and learn how each agency can support the other through the sharing of information, expertise and resources. The training initiative also encourages participants to develop a Memorandum of Understanding to codify joint response plans and information sharing protocols. The FBI and CDC also released an updated edition of the FBI/CDC Criminal and Epidemiological Joint Investigation Handbook in 2011. This handbook serves as a joint investigation reference for personnel with potential involvement in a bioterrorism investigation

Final Rule Stage: Control of Communicable Diseases: Interstate Action: Final Action - To Be Determined

This rule focuses primarily on requirements relating to the reporting of deaths and illnesses onboard aircrafts traveling domestically, and the collection of specific traveler contact information for the purpose of CDC contacting travelers in the event of an exposure to a communicable disease.

Final Rule Stage: Control of Communicable Diseases: Foreign and Possessions Action: Final Action -To Be Determined

The final rule focuses primarily on requirements relating to the reporting of deaths and illnesses onboard aircrafts and ships, and the collection of specific traveler contact information for the purpose of CDC contacting travelers in the event of an exposure to a communicable disease.

Guidance for Enhancing Personnel Reliability and Strengthening the Culture of Responsibility This report, which is a follow-up to the National Science Advisory Board for Biosecurity (NSABB) May 2009 report on personnel reliability, was undertaken in response to the U.S. government's request for specific strategies and guidance on practices that promote a culture of Page 244 of 276 responsibility with respect to biosecurity. The Board's recommendations address good management practices, the role of strong institutional and laboratory leadership and oversight, responsible hiring and employee management practices, and the need to assess that the effectiveness, potential impact, and unintended consequences of any measures being implemented. The report also discusses two potentially useful practices for enhancing personnel reliability and a culture of responsibility at the local level - video monitoring and the "two person rule" - that, while not recommended for broad implementation, should be considered by local institutions only after conducting an assessment of these practices' risks and impacts. The report also notes practices that the NSABB does not recommend for widespread implementation by institutions, particularly academic institutions.

The report is available at: http://oba.od.nih.gov/biosecurity/pdf/CRWG_Report_final.pdf

Implementation of a Decision Adopted Under the Australia Group (AG) Intersessional Silent Approval Procedures in 2010 and Related Editorial Amendments 15 CFR Parts 740, 742 and 774. The Bureau of Industry and Security, U.S. Department of Commerce, publishes this final rule to amend the Export Administration Regulations (EAR) to implement a decision based on a proposal that was discussed at the 2010 Australia Group (AG) Plenary and adopted under the AG intersessional silent approval procedures in November 2010. Specifically, this rule amends the Commerce Control List (CCL) entry in the EAR that controls human and zoonotic pathogens and "toxins,'' consistent with the intersessional changes to the AG's "List of Biological Agents for Export Control.'' First, this rule clarifies the scope of the AG- related controls in the EAR that apply to "South American haemorrhagic fever (Sabia, Flexal, Guanarito)'' and "Pulmonary and renal syndrome-haemorrhagic fever viruses (Seoul, Dobrava, Puumala, Sin Nombre)'' by revising the list of viruses in this CCL entry to remove these two fevers and replace them with ten viral causative agents for the fevers. These changes are intended to more clearly identify the causative agents that are of concern for purposes of the controls maintained by the AG. Second, this rule alphabetizes and renumbers the list of viruses in this CCL entry, consistent with the 2010 intersessional changes to the AG control list. Finally, this rule makes an editorial change to the CCL entry that controls human and zoonotic pathogens and "toxins.'' To assist exporters to more easily identify the bacteria and "toxins'' that are controlled under this CCL entry, this rule alphabetizes and renumbers the lists of bacteria and "toxins'' in the entry. This rule is effective September 12, 2011.

Implementation of the Understandings Reached at the 2010 Australia Group (AG) Plenary Meeting and Other AG-Related Clarifications and Corrections to the EAR 15 CFR Part 774. The Bureau of Industry and Security, U.S. Department of Commerce, publishes this final rule to amend the Export Administration Regulations (EAR) to implement the understandings reached at the June 2010 plenary meeting of the Australia Group (AG) and to make certain AG-related editorial clarifications and corrections to the EAR. Consistent with the June 2010 AG understandings, this rule amends the chemical manufacturing equipment entry on the Commerce Control List (CCL) of the EAR to reflect the addition of two parenthetical phrases that clarify the description of certain "materials'' contained in items on the AG "Control List of Dual-Use Chemical Manufacturing Facilities and Equipment and Related Technology and Software.'' In addition, this rule makes AG-related clarifications and corrections to the EAR. Specifically, this rule amends the human and zoonotic pathogens and toxins entry and the animal Page 245 of 276 pathogens entry on the CCL by making an update and a clarification that are consistent with the description of items on the AG "List of Biological Agents for Export Control'' and the AG "List of Animal Pathogens for Export Control,'' respectively. Finally, this rule amends the listing for "valves'' in the chemical manufacturing equipment entry on the CCL to clarify that it controls "valves'' for the "production'' of chemicals, as well as "valves'' for the "processing'' or "containment'' of chemicals. The purpose of this rule is to ensure that the AG-related entries on the CCL conform with the wording in the AG Control Lists (as updated by the understandings reached at the 2010 AG Plenary) and to clarify the meaning of terms used in these entries. This rule is effective April 20, 2011.

Notice of Proposed Rulemaking: Foreign Quarantine; Proposed Revision of Etiologic Agent Import Permit Program Action: Notice of Proposed Rulemaking, 14 October 2011

The Centers for Disease Control and Prevention (CDC) within the U.S. Department of Health and Human Services (HHS) is issuing this Notice of Proposed Rulemaking (NPRM) to revise the regulations that cover the importation of etiological agents and the hosts and vectors of human disease. The changes are proposed to improve CDC's ability to prevent the introduction, transmission, or spread of communicable diseases into the United States.

Proposed Changes to Security of Select Agents and Toxins (HHS, USDA, and DOJ) Under Executive Order 13546, "Optimizing the Security of Biological Select Agents and Toxins in the United States," a Federal Experts Security Advisory Panel (FESAP) was established to compose recommendations concerning the security of biological select agents and toxins (BSAT). The FBI was an active participant on the FESAP and co-chaired the working group charged with developing recommendations regarding personnel reliability and suitability. During 2011, the Department of Health and Human Services (HHS), the U.S. Department of Agriculture (USDA), and the Department of Justice (DOJ) submitted recommendations through the FESAP to the Deputy National Security Advisor for Homeland Security and Counterterrorism. Several of these recommendations require changes to the U.S. Federal Select Agent Program for implementation; others require the development of guidance for registered BSAT entities. Per Executive Order 13546, the goal is to have final regulatory changes published by October 2012. The 2011 recommendations included:

 A list of agents to be removed from the BSAT lists  A list of BSAT to be designated as "Tier 1" agents  Personnel Reliability and Suitability measures for "Tier 1" agents  Physical and cyber security measures for "Tier 1" agents  Further measures toward optimizing security practices for all entities possessing BSAT

Proposed Rule Stage: Control of Communicable Diseases: Foreign and Possessions Regulations; Nonhuman Primate Action: Final Action - July 2012

In this final rule, CDC will amend its regulations related to the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of cynomolgus, African Page 246 of 276 green, and rhesus monkeys to all NHPs. CDC will also reduce the frequency at which importers of the three species are required to renew their registrations, (from every 180 days to every two years) and incorporate existing guidelines into regulations. CDC will add new provisions to address NHPs imported as part of a circus or trained animal act, NHPs imported by zoological societies, the transfer of NHPs from approved laboratories, and non-live imported NHP products. Finally, all NHPs will be imported only through ports of entry where a CDC quarantine station is located.

Public Health Security and Bioterrorism Preparedness and Response Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List Action: Final Action October 2012

The Bioterrorism Preparedness Act requires that the HHS Secretary review and republish the list of select agents and toxins on at least a biennial basis. To assist with the biennial review, HHS reviewed recommendations provided by subject matter experts and the Intragovernmental Select Agents and Toxins Advisory Committee. In addition, on July 2, 2010, the President signed "Executive Order 13546: Optimizing the Security of Biological Select Agents and Toxins in the United States" to review, tier, and reduce the Select Agent List; establishing personal reliability standards for BSAT workers; and establishing physical security standards for identified Tier 1 select agents and toxins. This final rule implements the Executive Order and updates the list of select agents and toxins.

Select Agent Program Guidance The Select Agent Program issues guidance to Responsible Officials of Select Agent registered entities to assist entities with complying with the requirements of the Select Agent regulations. Guidance issued in 2011 included

 Additional Guidance Regarding Long Term Storage (9 June 2011)  Animals Injected with or Exposed to a Select Toxin (19 April 2011)  Authorization of Individual's Access Approval to Select Agents and Toxins to be Valid for a Period of Three Years (27 May 2011)  Botulinum neurotoxin producing species of Clostridium (16 August 2011)  Federal Experts Security Advisory Panel's Recommendations (21 June 2011)  Guidance for the Inactivation of Select Agents and Toxins and Rendering Samples Free of Select Agents and Toxins (14 December 2011)  Guidance on Containment Work with Eastern Equine Encephalitis (25 August 2011)  Guidelines for Avian Influenza Viruses (16 November 2011)  Hand Delivery of Packages Containing Select Agents and Toxins (1 April 2011)  Policy on BMBL 5th Edition Laboratory Facilities (Secondary Barrier) Standards (5 August 2011)  Posting of Agents and Toxins Incident Response Plan(3 June 2011)  Progress with Executive Order 13546: Optimizing the Security of Biological Select Agents and Toxins in the United States (9 March 2011)  Reporting Incidents Involving Select Agents and Toxins (1 April 2011)  Update to the FBI's Investigation [involving a suspicious package](7 January 2011) Page 247 of 276

A complete list of all of the guidance issued to date is available at the Select Agent Program website: http://www.selectagents.gov/SA_Gram.html

Strategies to Educate Amateur Biologists and Scientists in Non-Life Science Disciplines About Dual-Use Research in the Life Sciences In addition to its standing charge to advise on strategies and tools to promote awareness of the dual use issue in the life sciences community generally, the U.S. government charged the National Science Advisory Board for Biosecurity (NSABB) with developing recommendations for promoting awareness of the dual use issue among two non-traditional audiences for these efforts: (1) scientists trained in non-life science fields who collaborate in the life sciences on such endeavors and synthetic biology, and (2) amateur biologists who pursue life science research as an avocation and whose activities are becoming increasingly sophisticated. Toward that end, the NSABB has developed a report that presents a series of observations about the special characteristics of these communities and pairs them with recommendations for specially tailored strategies for awareness building. Available at: http://oba.od.nih.gov/biosecurity/pdf/FinalNSABBReport-AmateurBiologist- NonlifeScientists_June-2011.pdf

Updates to the Federal Experts Security Advisory Panel Recommendations Concerning the Select Agent Program The Federal Experts Security Advisory Panel (FESAP) was created in July 2010 by Executive Order (EO) 13546, "Optimizing the Security of Biological Select Agents and Toxins in the United States," and tasked to make recommendations regarding the biosecurity measures of the national Select Agent Program (SAP). The FESAP has carefully deliberated and developed recommendations, drawing on the work of previous federal and non-federal working groups and input from practitioners. The FESAP report contains recommendations, which in and of themselves, do not change any current policies, guidance, or regulations regarding the SAP. Part of EO 13546 requires the SAP to address FESAP recommendations during their next round of revisions to the Select Agent Regulations. FESAP recommendations (released June 2011) are available at: http://www.phe.gov/Preparedness/legal/boards/fesap/Documents/fesap- recommendations-101102.pdf

SAP proposed rule (published October 2011 in the Federal Register Vol. 76, No. 191) is available online at: http://www.gpo.gov/fdsys/pkg/FR-2011-10-03/html/2011-25427.htm

Page 248 of 276

Form G

BWC - Confidence Building Measure

Declaration of Vaccine Production Facilities

United States of America

9 July 2012 Page 249 of 276

Form G

Declaration of vaccine production facilities

The following website is provided by the US Food and Drug Administration as a reference for a current list of vaccines licensed in the United States and associated production facilities: http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm

Data provided in CBM Form G constitute excerpts from the information provided on the publicly available website listed above (as accessed on 25 February 2012). Trade names are included when provided by the manufacturer. Specific and current information about the vaccine and contact information for the manufacturer is available by following the hyperlinks provided on the above website. Page 250 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Barr Laboratories, Inc. 2. Location (Mailing Address)

2150 Perrowville Road Forest, Virginia 24551

3. General description of the types of diseases covered:

Adenovirus Type 4 and Type 7 Vaccine, Live, Oral

Vaccines: • Adenovirus Type 4 and Type 7 Vaccine, Live, Oral

Page 251 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Emergent BioDefense Operations Lansing, Inc. 2. Location (Mailing Address)

3500 N. Martin Luther King Jr. Blvd. Lansing, Michigan 48906

3. General description of the types of diseases covered:

Anthrax disease caused by Bacillus anthracis

Vaccines: • Anthrax Vaccine Adsorbed - [BioThrax]

Page 252 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

MassBiologics 2. Location (Mailing Address)

University of Massachusetts Medical School Boston, Massachusetts 02130

3. General description of the types of diseases covered:

Diphteria and tetanus caused by Corynebacterium diphtheriae and Clostridium tetani.

Vaccines: • Tetanus and Diphtheria Toxoids Adsorbed

Page 253 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

MedImmune LLC 2. Location (Mailing Address)

One MedImmune Way Gaithersburg, Maryland 20878

3. General description of the types of diseases covered:

Influenza disease caused by pandemic (H1N1) 2009 virus. Influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.

Vaccines: • Influenza A (H1N1) 2009 Monovalent Vaccine • Influenza Vaccine Live, Intranasal - [FluMist]

Page 254 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Merck & Co, Inc (NJ) 2. Location (Mailing Address)

One Merck Drive P.O. Box 100 Whitehouse Station, New Jersey 08889-0100

3. General description of the types of diseases covered:

Invasive disease caused by Haemophilus influenzae type b; infection caused by all known subtypes of hepatitis B virus; Hepatitis A disease; cervical, vulvar and vaginal cancer and certain other diseases caused by Human Papillomavirus (HPV) Types 6, 11, 16, and 18; Measles (rubeola); Mumps; diseases caused by Streptococcus pneumoniae; Rotavirus disease; Rubella (German measles) disease; Varicella disease caused by the varicella-zoster virus (VZV); Herpes zoster (shingles) disease.

Vaccines: • Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) - [PedvaxHIB] • Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) & Hepatitis B (Recombinant) Vaccine - [COMVAX] • Hepatitis A Vaccine, Inactivated - [VAQTA] • Hepatitis B Vaccine (Recombinant) - [Recombivax HB] • Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant - [Gardasil] • Measles, Mumps, and Rubella Virus Vaccine, Live - [M-M-R II] • Measles, Mumps, Rubella and Varicella Virus Vaccine Live - [ProQuad] • Pneumococcal Vaccine, Polyvalent - [Pneumovax 23] • Rotavirus Vaccine, Live, Oral, Pentavalent - [RotaTeq] • Varicella Virus Vaccine Live - [Varivax] • Zoster Vaccine, Live, (Oka/Merck) - [Zostavax]

Page 255 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Organon Teknika Corporation LLC 2. Location (Mailing Address)

100 Rodolphe Street Building 1300 Durham, North Carolina 27712

3. General description of the types of diseases covered:

For the prevention of tuberculosis in persons not previously infected with M. tuberculosis who are at high risk for exposure; For the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder; For the prophylaxis of primary or recurrent state Ta and/or T1 papillary tumors following transurethral resection (TUR).

Vaccines: • BCG Live vaccine - [BCG Vaccine; TICE BCG]

Page 256 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Sanofi Pasteur Biologics Co. 2. Location (Mailing Address)

38 Sidney Street Cambridge, Massachusetts 02139

3. General description of the types of diseases covered:

Smallpox disease

Vaccines: • Smallpox (Vaccinia) Vaccine, Live - [ACAM2000]

Page 257 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Sanofi Pasteur, Inc 2. Location (Mailing Address)

Discovery Drive Swiftwater, Pennsylvania 18370

3. General description of the types of diseases covered:

Diphtheria caused by Corynebacterium diphtheria; tetanus caused by Clostridium tetani; pertussis diseases; influenza disease caused by pandemic (H1N1) 2009 virus; influenza disease caused by H5N1 subtype; influenza disease caused by influenza virus subtypes A and type B; invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135; meningitis and meningococcemia caused by N. meningitidis; and Yellow fever acute viral illness caused by a mosquito-borne flavivirus.

Vaccines: • Diphtheria & Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed - [Tripedia; DTaP] • Diphtheria and Tetanus Toxoids Adsorbed • Influenza A (H1N1) 2009 Monovalent Vaccine • Influenza Virus Vaccine, H5N1 (for National Stockpile) • Influenza Virus Vaccine, Trivalent, Types A and B33 - [Fluzone® and Fluzone High- Dose] • Meningococcal Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine - [Menactra®] • Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined - [Menomune®-A/C/Y/W-1351] • Tetanus and Diphtheria Toxoids Adsorbed • Tetanus and Diphtheria Toxoids Adsorbed for Adult Use - [DECAVAC] • Tetanus Toxoid Adsorbed • Tetanus Toxoid for Booster Use Only • Yellow Fever Vaccine - [YF-VAX®]

Page 258 of 276

Form G

Declaration of vaccine production facilities

1. Name of facility

Wyeth Pharmaceuticals Inc 2. Location (Mailing Address)

Pfizer, Inc., 235 East 42nd Street New York, New York 10017

3. General description of the types of diseases covered:

Invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F and 23F.

Vaccines: • Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) - [Prevnar 13] • Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein) - [Prevnar]

Page 259 of 276

Appendix A

Biological Select Agents and Toxins

Biological Select Agents and Toxins are biological pathogens and toxins that the United States has determined have the potential to pose a severe threat to public health and safety, animal and plant health, or animal and plant products. The possession, use, and transfer of these agents is regulated by the U.S. Department of Health and Human Services (HHS) Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service under the Select Agent Regulations found in Part 73 of Title 42 of the Code of Federal Regulations, Part 331 of Title 7 of the Code of Federal Regulations, and Part 121 of Title 9 of the Code of Federal Regulations.

Information on Biological Select Agents and Toxins can be found on the National Select Agent Registry website: http://www.selectagents.gov/

HHS Select Agents and Toxins Abrin Saxitoxin Botulinum neurotoxins Shiga-like ribosome inactivating proteins Botulinum neurotoxin producing species of Shigatoxin Clostridium South American Haemorrhagic Fever viruses Cercopithecine herpesvirus 1 (Herpes B virus) • Flexal Clostridium perfringens epsilon toxin • Guanarito • Junin Coccidioides posadasii/Coccidioides immitis • Machupo Conotoxins • Sabia Coxiella burnetii Staphylococcal enterotoxins Crimean-Congo haemorrhagic fever virus T-2 toxin Diacetoxyscirpenol Tetrodotoxin Eastern Equine Encephalitis virus Tick-borne encephalitis complex (flavi) Ebola virus viruses Francisella tularensis • Central European Tick-borne Lassa fever virus encephalitis • Far Eastern Tick-borne encephalitis Marburg virus • Kyasanur Forest disease Monkeypox virus • Omsk Hemorrhagic Fever Reconstructed replication competent forms of • Russian Spring and Summer the 1918 pandemic influenza virus containing encephalitis any portion of the coding regions of all eight Variola major virus (Smallpox virus) gene segments (Reconstructed1918 Influenza Variola minor virus (Alastrim) virus) Yersinia pestis Ricin Rickettsia prowazekii Page 260 of 276

Rickettsia rickettsii

OVERLAP Select Agents and Toxins Bacillus anthracis Burkholderia pseudomallei (formerly Brucella abortus Pseudomonas pseudomallei) Brucella melitensis Hendra virus Brucella suis Nipah virus Burkholderia mallei ( formerlyPseudomonas Rift Valley fever virus mallei) Venezuelan Equine Encephalitis virus

USDA Select Agents and Toxins African horse sickness virus Menangle virus African swine fever virus Mycoplasma capricolum subspecies Akabane virus capripneumoniae (contagious caprine Avian influenza virus (highly pathogenic) pleuropneumonia) Bluetongue virus (exotic) Mycoplasma mycoides subspecies mycoides small colony (Mmm SC) (contagious bovine Bovine spongiform encephalopathy agent pleuropneumonia) Camel pox virus Peste des petits ruminants virus Classical swine fever virus Rinderpest virus Ehrlichia ruminantium (Heartwater) Sheep pox virus Foot-and-mouth disease virus Swine vesicular disease virus Goat pox virus Vesicular stomatitis virus (exotic): Indiana Japanese encephalitis virus subtypes VSV-IN2, VSV-IN3 Lumpy skin disease virus Virulent Newcastle disease virus 1

Malignant catarrhal fever virus (Alcelaphine herpesvirus type 1)

USDA PLANT PROTECTION AND QUARANTINE (PPQ) Select Agents and Toxins Peronosclerospora philippinensis Sclerophthora rayssiae var zeae (Peronosclerospora sacchari) Synchytrium endobioticum Phoma glycinicola (formerly Pyrenochaeta Xanthomonas oryzae glycines) Xylella fastidiosa (citrus variegated chlorosis Ralstonia solanacearum race 3, biovar 2 strain) Rathayibacter toxicus

Page 261 of 276

Appendix A

NIAID Category A, B, and C Priority Pathogens The National Institute of Allergy and Infectious Disease (NIAID) categorization of pathogens identifies specific pathogens as priorities for additional research efforts as part of the NIAID biodefense research agenda.

Additional information on NIAID Category A, B, and C Priority Pathogens can be found on the NIAID Biodefense website: http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/research/Pages/CatA.aspx http://www.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/Documents/categorybandc.pdf as well as: http://funding.niaid.nih.gov/ncn/glossary/default5.htm http://pathema.jcvi.org/pathema/AbcGenomes.shtml http://www.fas.org/irp/threat/cbw/niaid0803.pdf

Category A Bacteria • Bacillus anthracis (Anthrax) • Francisella tularensis (Tularemia) • Clostridium botulinum (Botulism) • Yersinia pestis (Plague)

Viruses • Variola major (Smallpox) and other pox • Machupo virus viruses • Bunyaviruses • Viral hemorrhagic fevers • Arenaviruses • Hantaviruses • Guanarito virus • Rift Valley fever virus • Junin virus • Flaviruses • Lassa virus • Dengue fever viruses • Lymphocytic choriomeningitis virus • Filoviruses • Marburg virus • Ebola virus

Category B Bacteria • Burkholderia pseudomallei • Food and Waterborne Pathogens • Burkholderia mallei (Glanders) • Escherichia coli O157:H7 • Clostridium perfringens (Epsilon toxin) • Vibrio cholerae (Cholera) • Coxiella burnetii (Q fever) • Salmonella species • Brucella melitensis, abortus, suis, and canis • Shigella species • Staphylococcus aureus (Enterotoxin B) • Listeria monocytogenes • Rickettsia prowazekii • Campylobacter jejuni • Chlamydia psittaci • Yersinia enterocolitica

Page 262 of 276

Viruses • Viral encephalitis • La Crosse virus • West Nile virus • Japanese encephalitis virus • Eastern equine encephalitis virus • Kyasanur forest virus • Western equine encephalitis virus • California encephalitis viruses • Venezuelan equine encephalitis virus • Food and Waterborne Pathogens • Hepatitis A virus (Hepatitis A) • Caliciviruses (Gastroenteritis)

Protozoa • Food and Waterborne Pathogens • Cryptosporidium parvum • Cyclospora cayatanensis • Giardia lamblia • Entamoeba histolytica • Toxoplasma gondii • Microsporidia Plants • Ricinus communis Castor bean (Ricin toxin)

Category C Emerging infectious disease threats such as Nipah virus and additional hantaviruses. NIAID priority areas: Bacteria • Coccidioides immitis (added February 2008) • Coccidioides posadasii (added February 2008) • Mycobacterium tuberculosis (including multidrug-resistant Tuberculosis) • Other Rickettsia Viruses • Chikungunya virus • Tickborne hemorrhagic fever viruses • Influenza viruses • Crimean-Congo hemorrhagic fever virus • Nipah virus • Tickborne encephalitis viruses • Rabies virus • Yellow fever virus • Severe acute respiratory syndrome associated • Other Hantaviruses coronavirus (SARS-CoV)

Prions Antimicrobial resistance, excluding research on sexually transmitted organisms* • Research on mechanisms of antimicrobial resistance • Studies of the emergence and/or spread of antimicrobial resistance genes within pathogen populations • Studies of the emergence and/or spread of antimicrobial-resistant pathogens in human populations Page 263 of 276

• Research on therapeutic approaches that target resistance mechanisms • Modification of existing antimicrobials to overcome emergent resistance

Antimicrobial research, as related to engineered threats and naturally occurring drug-resistant pathogens, focused on development of broad-spectrum antimicrobials Innate immunity, defined as the study of nonadaptive immune mechanisms that recognize, and respond to, microorganisms, microbial products, and antigens

*NIAID Category C Antimicrobial Resistance-Sexually Transmitted Excluded Organisms Bacterial vaginosis, Chlamydia trachomatis, Cytomegalovirus, Granuloma inguinale, Hemophilus ducreyi, Hepatitis B virus, Hepatitis C virus, Herpes Simplex virus, Human immunodeficiency virus, Human papillomavirus, Neisseria gonorrhea, Treponema pallidum, Trichomonas vaginalis Page 264 of 276

Appendix B

Compiled list of biological agents and toxins used for biodefense research

Biological Agents

Abrus precartorious (plant which produces abrin toxin) Acanthamoeba castellanii Acetivibrio ethanolgignens Achromobacter xylosoxidans Acidithiobacillus spp. Acinetobacter baumannii Actinobacillus equuli Actinobacillus lignieresii Actinobacillus pleuropneumoniae Actinomyces naeslundii Adenoviruses Adenovirus (recombinant) Adenovirus type 5 Aerococcus viridans Aeromonas hydrophila African swine fever virus (ASVF) Alcaligenes faecalis Algae: Achnanthes sp. Botryoccus sp. Chlamydomonas sp. Chlorella sp. Duneliella sp. Galdieria sp. Haematococcus sp. Isochrysis sp. Navicula sp. Neochloris sp. Nitzschia spp. Prymnesium spp. Alternaria spp. Anaerobiospirillum Anaeroplasma Aneurinibacillus migulanus Aspergillus flavus Aspergillus niger Aspergillus versicolor (attenuated) Avian influenza virus Highly Pathogenic Avian Influenza (HPAI) virus Highly Pathogenic Avian Influenza (HPAI) virus (recombinant vaccine reference strains of H5N1 and H5N3 subtypes) Avian metapneumonvirus Bacille Calmette-Guérin Bacillus anthracis Bacillus anthracis (attenuated) Bacillus anthracis (inactivated and vaccine strains only) Bacillus anthracis (inactivated) Bacillus anthracis (strains lacking the virulence plasmid pX02) Bacillus anthracis (strains that are devoid of both pX01 and pX02) Page 265 of 276

Bacillus anthracis Delta Stern Bacillus anthracis, genetic material Bacillus anthracis, protein Bacillus atrophaeus Bacillus brevis Bacillus cereus Bacillus cereus (inactivated and BSL-1 strains only) Bacillus cereus, genetic material Bacillus circulans Bacillus globigii Bacillus globigii [atrophaeus] spores Bacillus megaterium Bacillus mycoides Bacillus sphaericus Bacillus subtilis Bacillus subtilis, genetic material Bacillus subtilis variant niger Bacillus thuringiensis (Bt) Bacillus thuringiensis israelensis (Bti) Bacillus thuringiensis Al Hakam Bacillus thuringiensis, genetic material Bacillus thuringiensis kurstaki (Btk) Bacillus thuringiensis, protein Bacteriophage Bacteriophage MS2 Bacteriophage Q-beta Bacteriophage T4 Bacteroides fragilis Bartonella henselae Bifidobacterium dentium Bluetongue virus (BTV) Bluetongue virus (BTV), genetic material Border disease virus Bordetella avium Bordetella bronchiseptica Bordetella hinzii Bordetella pertussis Borrelia burgdorferi Borrelia crocidurae Borrelia turicatae Botulinum neurotoxin producing species Bovine adenovirus Bovine calicivirus Bovine herpes and retroviruses: Untyped Bovine herpesvirus Bovine lentivirus Page 266 of 276

Bovine papular stomatitis, genetic material Bovine papular stomatitis virus Bovine parainfluenza virus Bovine parvovirus Bovine respiratory syncytial virus (BRSV) Bovine spumavirus Bovine viral diarrhea virus (BVDV) Brachyspira alvinipulli Brachyspira hyodysenteriae Brachyspira innocens Brachyspira pilosicoli Brucella (killed) Brucella abortus Brucella abortus (killed) Brucella abortus, genetic material Brucella canis Brucella canis, genetic material Brucella melitensis Brucella melitensis (inactivated) Brucella melitensis, genetic material Brucella neotomae Brucella ovis Brucella spp. Brucella suis Brucella suis, genetic material Brugia malayi Bujaru virus Bunyamwera virus Burkholderia andropogonis Burkholderia caryophylli Burkholderia cepacia Burkholderia gladioli Burkholderia glumae Burkholderia mallei Burkholderia mallei (inactivated) Burkholderia mallei (killed) Burkholderia pseudomallei Burkholderia spp. Burkholderia spp., genetic material Burkholderia spp., protein Burkholderia thailandesis Camel pox virus (CMPV) Campylobacter coli Campylobacter fetus Campylobacter jejuni Campylobacter jejuni (killed), nucleic acid Page 267 of 276

Campylobacter lari Campylobacter sputorum Candiru virus Canine calicivirus Canine coronavirus Canine Distemper virus Canine parvovirus Caprine adenovirus Caprine herpervirus, genetic material Caprine herpesvirus Caprine lentivirus Caprine respiratory syncytial virus Caulobacter vibrioides Cedecea neteri Central European Tick-borne encephalitis virus Cercopithecine herpesvirus Chaetomium globosum Chapare virus Chikungunya virus Chilibre virus Chlamydia pneumoniae Chlamydia psittaci Chlamydia trachomatis Chlorella pyrenoidosa Chlorella sorokiniana Chromobacterium violaceum Chronic wasting disease Chryseobacterium spp. Cladosporium cladosporioides Classical swine fever virus (CSFV) Classical swine fever virus (CSFV), genetic material Clavibacter michiganense Clostridium argentinense Clostridium botulinum Clostridium botulinum (inactivated) Clostridium botulinum, botulinum neurotoxin producing species Clostridium butyricum Clostridium difficile Clostridium novyi Clostridium perfringens Clostridium perfringens, inactivated nucleic acid Clostridium septicum Clostridium sordelli Clostridium sporogenes Clostridium tetani Clostridium tetani, inactivated nucleic acid Page 268 of 276

Coccidiodes immitis Coccidioides posadasii Colorado tick fever virus Corona virus Corynebacterium bovis Corynebacterium pseudotuberculosis Corynebacterium spp. Cowpox virus (CPXV) Coxiella burnetii Coxiella burnetii (inactivated) Coxiella burnetii (killed) Coxiella burnetii, genetic material Coxiella burnetii, inactivated, nucleic acid Coxsackievirus Crimean-Congo hemorrhagic fever (CCHF) virus Cytomegalovirus Deer adenovirus, genetic material Deinococcus radiodurans Dengue virus Dengue virus, nucleic acid Dengue/Langat Chimera Dengue/TBEV Chimera Dichomitus squalens E coli HB101 (viable) Eastern equine encephalitis virus (EEEV) (killed) Eastern equine encephalitis virus (EEEV) Eastern equine encephalitis virus (EEEV), genetic material Ebola virus Ebola virus (killed) Ebola virus, genetic material Ebola virus, protein Encephalomyocarditis virus Enteric viruses of poultry Enterobacter aerogenes Enterobacter cloacae Enterococcus casseliflavus envelope protein of dengue virus (protein) Epizootic hemorrhagic disease virus Equine adenovirus Equine arteritis virus Equine herpesvirus Equine herpesvirus, genetic material Erwinia herbicola Erwinia herbicola (inactivated) Erysipelothrix spp. Escherichia coli Page 269 of 276

Escherichia coli 0157:H7 Escherichia coli 0157:H7 (killed) Escherichia coli BL21 Escherichia coli K12 Far-Eastern tick-borne encephalitis virus Feline calicivirus Feline infectious peritonitis virus Feline parvovirus Flavobacterium mizutaii Flexal virus Foot and Mouth Disease (FMD) virus Foot and Mouth Disease (FMD) virus, genetic material Fort Morgan virus Francisella novicida Francisella novicida Utah 112 Francisella novicida-like isolates Francisella philomiragia Francisella philomiragia (inactivated) Francisella spp. Francisella tularensis Francisella tularensis (inactivated) Francisella tularensis (LVS) Francisella tularensis (subspecies holartica) Francisella tularensis (subspecies novicida) Francisella tularensis (vaccine strain) Francisella tularensis genetic material Francisella tularensis, protein Francisella tularensis Schu4 (CRP inactivated) Frijoles virus Fusarium oxysporum Fusobacterium Fusobacterium necrophorum Geobacillus stearothermophilus Goat pox virus Guanarito virus Haemophilus avium Haemophilus paragallinarium Haemophilus parainfluenzae Haemophilus parasuis Haemophilus somnus Hafnia alvei Hanta virus Helicobacter pylori Hemorrhagic enteritis virus Hendra virus Hepatitis B Virus (clinical sample) Page 270 of 276

Hepatitis C Virus (clinical sample) Herpes simplex virus Human immunodeficiency virus (HIV) Human noroviruses Human noroviruses, genetic material Infectious bursal disease virus (IBDV) Influenza virus Influenza virus (reconstructed 1918 ) -Reconstructed replication competent forms of the 1918 flu pandemic containing any portion of the coding regions of all eight gene segments Influenza virus A and B Japanese Encephalitis (JE) virus Junin virus Junin virus (vaccine strain Candid 1) Klebsiella pneumoniae Kluyvera ascorbata Kunjin virus Kyasanur Forest disease virus La Crosse virus Lactobacillus casei Lactobacillus lactus Langat virus Langat/TBEV chimera Lassa virus Legionella pneumophila Leishmania amazonensis Lentiviral vectors Lentivirus Bovine immunodeficiency virus Leptospira biflexa Leptospira borgpetersenii Leptospira inadai Leptospira interrogans Leptospira kirschneri Leptospira noguchii Leptospira santarosai Leptospira weilii Liberabacter africanus Liberabacter americanus Liberabacter asiaticus Listeria monocytogenes Lujo viros Lymphocytic Choriomeningitis virus (LCMV) Machupo virus Magnaporthe grisea Malignant cattarhal fever virus, genetic material Mannheimia glucosida Mannheimia haemolytica Page 271 of 276

Marburg virus Marburg virus (killed) Marburg virus, genetic material Marburg virus, protein Marek's disease herpesvirus Menangle virus Mink calicivirus Mobala virus Modified Vaccinia Ankara (MVA) virus Monkey pox virus Moose adenovirus Moraxella bovis Moraxella spp. Murid herpes virus Murine hepatitis virus Mycobacterium avium Mycobacterium bovis Mycobacterium bovis (BCG) vaccine Mycobacterium kansasii Mycobacterium paratuberculosis Mycobacterium smegmatis Mycobacterium tuberculosis Mycobacterium tuberculosis (drug resistant) Mycoplasma arginini Mycoplasma capricolum Mycoplasma conjunctivae Mycoplasma gallisepticum Mycoplasma ovipnuemoniae Mycoplasma putrefaciens Mycoplasma synoviae Naegleria fowleri Nannochloropsis Neisseria lactamica Neisseria spp. Neurospora crassa Newcastle disease virus (NDV) Nipah virus Odocoileus adenovirus Omsk Hemorrhagic Fever Orf virus Ornithobacterium rhinotracheale Ovine adenovirus Ovine lentiviruses Ovine parainfluenza virus Ovine respiratory syncytial virus Parainfluenza virus Page 272 of 276

Pasteurella canis Pasteurella dagmatis Pasteurella gallinarum Pasteurella haemolytica Pasteurella langae Pasteurella multocida Pasteurella pnuemotropica Pasteurella stomatis Pasteurella trehalosi Pasteurella ureae Penicillium chryogenum Penicillium funinculosum Peronosclerospora phillipinensis Peronosclerospora sacchari Phakopsora pachyrhizi Phanerochaete chrysosporium Phodobacter katedanii Phoma glycinicola (formerly Peronosclerospora sacchari) Phytophthora infestans Phytophthora kernoviae Phytophthora ramorum Pichinde virus Plum Pox Virus Porcine adenovirus Porcine astrovirus Porcine calicivirus Porcine circovirus Porcine enterovirus Porcine hemagglutinating encephalomyelitis virus Porcine parvovirus Porcine reovirus Porcine reproductive and respiratory syndrome virus (PRRS, Porcine arterivirus) Porcine respiratory coronavirus Powassan virus Prevotella nigrescens Prions Propionibacterium avidum Proteus spp. Pseudocowpox virus Pseudomonas aeruginosa Pseudomonas constantinii Pseudomonas fluroescens Pseudomonas oxalacticus Psittacine herpesvirus Puccinia graminis tritici Puccinia striiformis Page 273 of 276

Punta Toro virus Puumala virus Rabbit pox virus Ralstonia solanacearum Raracoccus marcusii Rathayibacter toxicus Respiratory syncytial virus (RSV) Rhino virus Rhizobium (Agrobacterium) radiobacter Rhodococcus equi Rhodococcus fasciens Rhodocuoccus erythropolis Rickettsia prowazekii Rickettsia prowazekii, genetic material Rickettsia rickettsii Rickettsia rickettsii, genetic material Rickettsia spp. Riemerella anatipestifer Rift Valley Fever (RVF) virus Rift Valley Fever Virus MP-12 Rinderpest virus, genetic material Russian Spring and Summer encephalitis virus Sabia virus Saccharomyces cerevisiae Salehebad virus Salmonella bongori Salmonella cholerasuis Salmonella dublin Salmonella enterica Salmonella enteritidis Salmonella pullorum Salmonella typhimurium Salmonella typhimurium (killed) San Miguel sea lion virus Sandfly Fever Naples virus Scrapie Semliki Forest virus Sendai virus Sendai virus (SeV) Serratia marcescens Severe Acute Respiratory Syndrome virus (SARS) Sheep pox virus Shewanella oneidensi Shigella dysenteriae Shigella dysenteriae (killed) Shigella ssp. Page 274 of 276

Simian Virus 40 Sindbis virus Skunk calicivirus Soybean Dwarf virus Sphingobacterium spp. Squirrel fibroma virus St. Louis encephalitis Staphylococcus aureus Staphylococcus aureus (inactivated) Staphylococcus epidermidis Staphylococcus hominis Staphylococcus intermedius Staphylococcus saprophyticus Streptococcus agalactiae Streptococcus bovis Streptococcus dysgalactiae ssp. Streptococcus intermedius Streptococcus intestinalis Streptococcus pneumoniae Streptococcus pyogenes Streptococcus uberis Streptomyces coelicolor Streptomyces lividans Suid herpesvirus, genetic material Sulfitobacter donghicola Swine enterovirus Swine influenza virus Tacaribe virus Tatlockia maceachernii Thermus aquaticus Tick-borne encephalitis virus Tick-borne flaviviruses Toxoplasma gondii Transmissible gastroenteritis virus Treponema bryantii Treponema denticola Treponema hyodysenteriae Treponema pallidum Treponema phagedenis Treponema succinifaciens Trypanosoma cruzi Uukuniemi virus Vaccinia virus Vaccinia virus (inactivated) Vaccinia virus (killed) Vaccinia Virus (Western Reserve) Page 275 of 276

Varicella zoster virus (VZV) Variola major virus (Smallpox virus) Venezuelan equine encephalitis (VEE) virus (inactivated) Venezuelan equine encephalitis (VEE) virus Venezuelan equine encephalitis (VEE) virus (killed) Venezuelan equine encephalitis (VEE) virus (TC83, attenuated) Venezuelan equine encephalitis (VEE) virus (vaccine strain TC-83) Venezuelan equine encephalitis (VEE) virus (attenuated) Venezuelan equine encephalitis (VEE) virus, genetic material Vesicular stomatitis virus (VSV) Vesicular Stomatitis Virus Indiana subtype 1 Vibrio cholerae Vibrio cholerae (killed) Vibrio fisheri Vibrio harveyi Wangiella dematidis Water buffalo adenovirus West Nile virus (WNV) West Nile virus (WNV), genetic material Western equine encephalitis (WEE) virus Western equine encephalitis (WEE) virus (killed) Xylella fastidiosa Yellow fever virus Yellow fever virus (17D) Yersinia bercovieri Yersinia enterocolitica Yersinia intermedia Yersinia pestis Yersinia pestis (inactivated) Yersinia pestis (killed) Yersinia pestis (KIM) Yersinia pestis (pgm- strain) (attenuated) Yersinia pestis (Lcr- strains) Yersinia pestis (pgm-strain) Yersinia pestis D27, inactivated nucleic acid Yersinia pestis, genetic material Yersinia pseudotuberculosis Yersinia pseudotuberculosis (inactivated) Yersinia rohdei Yersinia ruckeri Yersinia spp. Page 276 of 276

Toxins and Toxoids

Abrin Aflatoxin Agatoxin Anthrax Toxin Bacillus thurigiensis konkukian Botulinum Toxoid Brevetoxin California encephalitis virus Caulobacter vibriodes Cholera toxin Clostridium botulinum neurotoxin A Clostridium botulinum neurotoxin Clostridium botulinum neurotoxin (inactivated) Clostridium botulinum toxoids [not toxins] Clostridium perfringens epsilon toxin Clostridium tetani toxin Conotoxin Conotoxins (mu-conotoxins: sodium channel antagonist) Deoxynivalenol Diacetoxyscirpenol Diphtheria toxin Domoic acid Fumonisin Marine toxins Microcystin LR Neosaxitoxin Ochratoxin Pertussis toxin Ricin Ricin (inactivated) Ricin A chain Saxitoxin Shiga toxin 1 and 2 Shiga-like ribosome inactivating proteins Shigatoxin Staphylococcal enterotoxin Staphylococcal enterotoxin B (SEB) toxoid T-2 toxin Tetrodotoxin