Taï Forest Virus Does Not Cause Lethal Disease in Ferrets
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A Multicenter, Multi-Outbreak, Randomized, Controlled Safety And
2018 Ebola MCM RCT Protocol Page 1 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 A Multicenter, Multi-Outbreak, Randomized, Controlled Safety and Efficacy Study of Investigational Therapeutics for the Treatment of Patients with Ebola Virus Disease Short Title: 2018 Ebola MCM RCT Protocol Sponsored by: Office of Clinical Research Policy and Regulatory Operations (OCRPRO) National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Bethesda, MD 20892 NIH Protocol Number: 19-I-0003 Protocol IND #: 125530 ClinicalTrials.gov Number: NCT03719586 Date: 4 October 2019 Version: 7.0 CONFIDENTIAL This document is confidential. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the study sponsor and principal investigator. 2018 Ebola MCM RCT Protocol Page 2 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 KEY ROLES DRC Principal Investigator: Jean-Jacques Muyembe-Tamfum, MD, PhD Director-General, DRC National Institute for Biomedical Research Professor of Microbiology, Kinshasa University Medical School Kinshasa Gombe Democratic Republic of the Congo Phone: +243 898949289 Email: [email protected] Other International Investigators: see Appendix E Statistical Lead: Lori Dodd, PhD Biostatistics Research Branch, DCR, NIAID 5601 Fishers Lane, Room 4C31 Rockville, MD 20852 Phone: 240-669-5247 Email: [email protected] U.S. Principal Investigator: Richard T. Davey, Jr., MD Clinical Research Section, LIR, NIAID, NIH Building 10, Room 4-1479, Bethesda, -
Rabbit Anti-Marburgvirus (MARV) VLP Pab ELISA Data
4 Research Court, Suite 300 Rockville, MD 20850 877-411-2041 [email protected] Rabbit anti-Marburgvirus (MARV) VLP pAb ELISA Data: Catalog #: 04-0005 IgG IgG + IgG + Lot #: MMIG201001IBT Dilution MMARV ZEBOV 1:X Antigen Antigen Immunogen: MARV (Musoke strain) Virus-like Particles (VLPs) containing glycoprotein (GP) 1000 3.30 2.66 Nucleoprotein (NP), and viral protein (VP40). 3162 3.07 1.80 10000 2.68 0.89 Description: Protein A purified rabbit polyclonal 31623 1.87 0.37 antibody reactive to MARV VLP raised in New 100000 0.99 0.14 Zealand white rabbits. 316228 0.43 0.05 1000000 0.17 0.02 Supplied: 0.5 mg of antibody is supplied in PBS at a concentration of 5.75 mg/mL. 0.01% Sodium azide has been added. -Antigen is coated on ELISA plates overnight. -Add 200µl blocking buffer then wash wells with Clonality: Polyclonal PBST. -Antiserum is diluted semi-log. Relevance: the filovirus Marburgvirus is a -Incubate antibody for 2 hour. Category A (NIAID) and HHS select agent. -Wash unbound antibodies and add HRP- Recommended Dilutions: conjugated anti-rabbit IgG. -Wash plates and add substrate to develop color for ELISA: Assay-dependent dilution. 20 minutes. WB: Assay-dependent dilution -Read absorbance at 650nm. Amount of color is directly proportional to amount of antibodies. Storage: 2-3 weeks +4oC, -20◦C long term Western Blot Cross Reactivity: Historical data showed some cross-reactivity with Ebola Virus (EBOV) and -Antiserum recognizes Marburg musoke Sudan Virus (SUDV) VLP’s, most likely due to glycoprotein, nucleoprotein, and VP40 antibodies against Baculovirus proteins since the VLP’s were expressed in SF9-Baculovirus system. -
MARBURG HEMORRHAGIC FEVER (Marburg HF)
MARBURG HEMORRHAGIC FEVER (Marburg HF) REPORTING INFORMATION • Class A: Report immediately via telephone the case or suspected case and/or a positive laboratory result to the local public health department where the patient resides. If patient residence is unknown, report immediately via telephone to the local public health department in which the reporting health care provider or laboratory is located. Local health departments should report immediately via telephone the case or suspected case and/or a positive laboratory result to the Ohio Department of Health (ODH). • Reporting Form(s) and/or Mechanism: o Immediately via telephone. o For local health departments, cases should also be entered into the Ohio Disease Reporting System (ODRS) within 24 hours of the initial telephone report to the ODH. • Key fields for ODRS reporting include: import status (whether the infection was travel-associated or Ohio-acquired), date of illness onset, and all the fields in the Epidemiology module. AGENT Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. Caused by a genetically unique zoonotic RNA virus of the family Filoviridae, its recognition led to the creation of this virus family. The five species of Ebola virus are the only other known members of the family Filoviridae. Marburg virus was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia). A total of 31 people became ill, including laboratory workers as well as several medical personnel and family members who had cared for them. -
A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures
viruses Communication A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures Ryan P. Bennett 1,† , Courtney L. Finch 2,† , Elena N. Postnikova 2 , Ryan A. Stewart 1, Yingyun Cai 2 , Shuiqing Yu 2 , Janie Liang 2, Julie Dyall 2 , Jason D. Salter 1 , Harold C. Smith 1,* and Jens H. Kuhn 2,* 1 OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA; [email protected] (R.P.B.); [email protected] (R.A.S.); [email protected] (J.D.S.) 2 NIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA; courtney.fi[email protected] (C.L.F.); [email protected] (E.N.P.); [email protected] (Y.C.); [email protected] (S.Y.); [email protected] (J.L.); [email protected] (J.D.) * Correspondence: [email protected] (H.C.S.); [email protected] (J.H.K.); Tel.: +1-585-697-4351 (H.C.S.); +1-301-631-7245 (J.H.K.) † These authors contributed equally to this work. Abstract: Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody- based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. -
MARBURG VIRUS [African Hemorrhagic Fever, Green Or Vervet Monkey Disease]
MARBURG VIRUS [African Hemorrhagic Fever, Green or Vervet Monkey Disease] SPECIES: Nonhuman primates, especially african green monkeys & macaques AGENT: Agent is classified as a Filovirus. It is an RNA virus, superficially resembling rhabdoviruses but has bizarre branching and filamentous or tubular forms shared with no other known virus group on EM. The only other member of this class of viruses is ebola virus. RESERVOIR AND INCIDENCE: An acute highly fatal disease first described in Marburg, Germany in 1967. Brought to Marburg in a shipment of infected African Green Monkeys from Uganda. 31 people were affected and 7 died in 1967. Exposure to tissue and blood from African Green monkeys (Cercopithecus aethiops) or secondary contact with infected humans led to the disease. No disease occurred in people who handled only intact animals or those who wore gloves and protective clothing when handling tissues. A second outbreak was reported in Africa in 1975 involving three people with no verified contact with monkeys. Third and fourth outbreaks in Kenya 1980 and 1987. Natural reservoir is unknown. Monkeys thought to be accidental hosts along with man. Antibodies have been found in African Green monkeys, baboons, and chimpanzees. 100% fatal in experimentally infected African Green Monkeys, Rhesus, squirrel monkeys, guinea pigs, and hamsters. TRANSMISSION: Direct contact with infected blood or tissues or close contact with infected patients. Virus has also been found in semen, saliva, and urine. DISEASE IN NONHUMAN PRIMATES: No clinical signs occur in green monkeys, but the disease is usually fatal after experimental infection of other primate species. Leukopenia and petechial hemorrhages throughout the body of experimentally infected monkeys, sometimes with GI hemorrhages. -
To Ebola Reston
WHO/HSE/EPR/2009.2 WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 EPIDEMIC AND PANDEMIC ALERT AND RESPONSE WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 © World Health Organization 2009 All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distin- guished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the policies of the World Health Organization. -
How Severe and Prevalent Are Ebola and Marburg Viruses?
Nyakarahuka et al. BMC Infectious Diseases (2016) 16:708 DOI 10.1186/s12879-016-2045-6 RESEARCHARTICLE Open Access How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence Luke Nyakarahuka1,2,5* , Clovice Kankya2, Randi Krontveit3, Benjamin Mayer4, Frank N. Mwiine2, Julius Lutwama5 and Eystein Skjerve1 Abstract Background: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24–100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Methods: Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. Results: The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0–76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5–80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%–11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5–2.0%, I2 = 94.8%). -
Development of an Antibody Cocktail for Treatment of Sudan Virus Infection
Development of an antibody cocktail for treatment of Sudan virus infection Andrew S. Herberta,b, Jeffery W. Froudea,1, Ramon A. Ortiza, Ana I. Kuehnea, Danielle E. Doroskya, Russell R. Bakkena, Samantha E. Zaka,b, Nicole M. Josleyna,b, Konstantin Musiychukc, R. Mark Jonesc, Brian Greenc, Stephen J. Streatfieldc, Anna Z. Wecd,2, Natasha Bohorovae, Ognian Bohorove, Do H. Kime, Michael H. Paulye, Jesus Velascoe, Kevin J. Whaleye, Spencer W. Stoniera,b,3, Zachary A. Bornholdte, Kartik Chandrand, Larry Zeitline, Darryl Sampeyf, Vidadi Yusibovc,4, and John M. Dyea,5 aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; bThe Geneva Foundation, Tacoma, WA 98402; cFraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711; dDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; eMapp Biopharmaceutical, Inc., San Diego, CA 92121; and fBioFactura, Inc., Frederick, MD 21701 Edited by Y. Kawaoka, University of Wisconsin–Madison/University of Tokyo, Madison, WI, and approved December 30, 2019 (received for review August 28, 2019) Antibody-based therapies are a promising treatment option for antibody-based immunotherapies. Subsequently, several indepen- managing ebolavirus infections. Several Ebola virus (EBOV)-specific dent groups reported the postexposure efficacy of monoclonal and, more recently, pan-ebolavirus antibody cocktails have been antibody (mAb)-based immunotherapies against EVD in ma- described. Here, we report the development and assessment of a caques when administered as mixtures of two or more mAbs (14–17). Sudan virus (SUDV)-specific antibody cocktail. We produced a panel These landmark studies demonstrated that combination mAb- of SUDV glycoprotein (GP)-specific human chimeric monoclonal based immunotherapies are a viable treatment option for EVD antibodies (mAbs) using both plant and mammalian expression and spurred therapeutic antibody development for filoviruses. -
Understanding Ebola
Understanding Ebola With the arrival of Ebola in the United States, it's very easy to develop fears that the outbreak that has occurred in Africa will suddenly take shape in your state and local community. It's important to remember that unless you come in direct contact with someone who is infected with the disease, you and your family will remain safe. State and government agencies have been making preparations to address isolated cases of infection and stop the spread of the disease as soon as it has been positively identified. Every day, the Centers of Disease Control and Prevention (CDC) is monitoring developments, testing for suspected cases and safeguarding our lives with updates on events and the distribution of educational resources. Learning more about Ebola and understanding how it's contracted and spread will help you put aside irrational concerns and control any fears you might have about Ebola severely impacting your life. Use the resources below to help keep yourself calm and focused during this unfortunate time. Ebola Hemorrhagic Fever Ebola hemorrhagic fever (Ebola HF) is one of numerous Viral Hemorrhagic Fevers. It is a severe, often fatal disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). Ebola HF is caused by infection with a virus of the family Filoviridae, genus Ebolavirus. When infection occurs, symptoms usually begin abruptly. The first Ebolavirus species was discovered in 1976 in what is now the Democratic Republic of the Congo near the Ebola River. Since then, outbreaks have appeared sporadically. There are five identified subspecies of Ebolavirus. -
Ebolavirus an Animals
Ebolavirus and Animals Our knowledge to date and how animal health can support the public health emergency Ebolavirus and Animals – Our knowledge to date and how animal health can support the public health emergency • 29 May 2018 Speakers • Lee Myers • Cyprien Felix Biaou Manager a.I. Emergency Management Livestock Development Officer, FAO Centre for Animal Health (EMC-AH) sub-regional Office for Central Africa Coordinator of FAO’s Ebola Incident (FAO-SFC) Coordination Group (ICG) • Claudia Pittiglio • Sophie von Dobschuetz Ecologist Global Surveillance coordinator (EPT-2) FAO Global Early Warning System (FAO- Emergency Prevention system for GLEWS) and Emerging Pandemic Threats transboundary Animal Diseases Programme Phase 2 (EPT-2) (EMPRES-AH) Ebolavirus and Animals – Our knowledge to date and how animal health can support the public health emergency • 29 May 2018 Webinar Content – Ebola and Animals • Presentation of FAO’s activities – Global level (Lee MYERS) – Regional and country levels (Cyprien BIAOU) • Susceptibility of animal species – Wildlife (Claudia PITTIGLIO) – Domestic (Sophie VON DOBSCHUETZ) • Availability of diagnostic tests for animal samples (Sophie VON DOBSCHUETZ) • What AH agencies and partners are doing (Sophie VON DOBSCHUETZ) Ebolavirus and Animals – Our knowledge to date and how animal health can support the public health emergency • 29 May 2018 3 Context of this webinar: <Phylogeny of the family Filoviridae ZEBOV Current outbreak in the Democratic Republic of the Congo (DRC) © Basicmedical Key Ebolavirus and Animals – Our knowledge to date and how animal health can support the public health emergency • 29 May 2018 FAO Ebola Incident Coordination Group (ICG) • In the spirit of One Health, FAO is supporting the efforts of the public health sector in response to the EVD outbreak in the Democratic Republic of the Congo. -
Risk Assessment and Risk Mitigation Review(S)
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761169Orig1s000 RISK ASSESSMENT and RISK MITIGATION REVIEW(S) Division of Risk Management (DRM) Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE) Center for Drug Evaluation and Research (CDER) Application Type BLA Application Number 761169 PDUFA Goal Date October 25, 2020 OSE RCM # 2020-264 Reviewer Name(s) Elizabeth Everhart, MSN, RN, ACNP Team Leader Naomi Boston, PharmD Acting Deputy Division Doris Auth, PharmD Director Review Completion Date August 10, 2020; date entered into DARRTS, August 20, 2020 Subject Evaluation of Need for a REMS Established Name atoltivimab – odesivimab – maftivimab (REGN-EB3) Trade Name Inmazeb Name of Applicant Regeneron Pharmaceuticals, Inc. Therapeutic Class Human IgG monoclonal antibody Formulation Solution for infusion Dosing Regimen 50 mg of each mAb/kg (3mL/kg) IV (b) (4) × 1 1 Reference ID: 4659652 Table of Contents EXECUTIVE SUMMARY ............................................................................................................................................................3 1 Introduction........................................................................................................................................................................3 2 Background .........................................................................................................................................................................3 2.1 Product Information..............................................................................................................................................3 -
761169Orig1s000
CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761169Orig1s000 OTHER REVIEW(S) LABEL AND LABELING REVIEW Division of Medication Error Prevention and Analysis (DMEPA) Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE) Center for Drug Evaluation and Research (CDER) *** This document contains proprietary information that cannot be released to the public*** Date of This Review: October 7, 2020 Requesting Office or Division: Division of Antivirals (DAV) Application Type and Number: BLA 761169 Product Name, Dosage Form, Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) and Strength: Injection 241.7 mg/241.7 mg/241.7 mg per 14.5 mL (16.67 mg/16.67 mg/16.67 mg per mL) Product Type: Multi-Ingredient Product Rx or OTC: Prescription (Rx) Applicant/Sponsor Name: Regeneron Pharmaceuticals, Inc. (Regeneron) FDA Received Date: February 25, 2020 OSE RCM #: 2020-263 DMEPA Safety Evaluator: Valerie S. Vaughan, PharmD DMEPA Associate Director of Mishale Mistry, PharmD, MPH Nomenclature and Labeling: 1 1 REASON FOR REVIEW As part of the approval process for Inmazeb injection, 241.7 mg/241.7 mg/241.7 mg per 14.5 mL (16.67 mg/16.67 mg/16.67 mg per mL), the Division of Antivirals (DAV) requested that we review the proposed labels and labeling for areas that may lead to medication errors. 2 MATERIALS REVIEWED We considered the materials listed in Table 1 for this review. The Appendices provide the methods and results for each material reviewed. Table 1. Materials Considered for this