DISCOVERY LABORATORY • CLINIC • COMMUNITY • WORLD Summer 2009

A Global Call To Action from HIV Co-Discoverers Robert Gallo and Luc Montagnier “HIV/AIDS Remains the Number One Global Health Threat” Robert C. On Friday, May 8, 2009 HIV 4. Enhance HIV/AIDS education co-discoverers Drs. Robert C. Gallo, and prevention, especially in director of the Institute of Human countries with high infection Virology at the University of Mary- rates land School of Medicine, and Luc A. 5. Support cutting-edge vaccine Montagnier, president of the World research and the development of Foundation for AIDS Research and new effective therapies Prevention, called on international 6. Continue the focus on preventing organizations and governments mother-to-child HIV transmis- to immediately implement six sion objectives to end the HIV/AIDS pandemic. They made the joint “Here we are, 25 years after announcement at the National Press discovering the cause of AIDS Club in Washington, D.C., which and we still have a major, public was preceded by comments from Montagnier and Gallo during the press conference. health HIV/AIDS crisis,” said Dr. Jeff Crowley, Director of the White Gallo. “Never in the history of House Office of National AIDS Policy. treatment and control programs along with mankind have we so quickly identified the “Globally, many are acting as though HIV regional research institutions in developing cause of an epidemic, developed a test for it and AIDS are no longer the threat they were countries and begun to develop drug therapy, changing a 25 years ago when the HIV virus was first 3. Cultivate and inspire young scientists in the once-deadly virus to a lifelong condition with field of human virology discovered. However, in fact they remain an Continued on page 3 unparalleled global health threat, and despite progress in treatment, could worsen unless determined action is taken. We believe the recommendations we are making today are DIRECTOR’S MESSAGE key to reducing and ultimately minimizing the Robert C. Gallo, MD devastation of HIV and AIDS,” said Drs. Gallo This time around, I wanted to present my Director’s January 22, 2009 and Montagnier. message differently. As many of you know our good Dear Marty, friend – also an IHV Board of Advisor member – and You have introduced me world-renowned HIV/AIDS patient advocate, Marty Global Call to Action: at meetings and some events Delaney, passed away at the end of January 2009. I and I have introduced you 1. Invest in medical infrastructure and edu- had been in touch with Marty since he became sick at others over the past few cational outreach programs in U.S. com- last fall. I thought sharing my last words to him would decades, but now it is time to munities most affected by the HIV/AIDS be a fitting tribute to my friendship with Marty, and bare my deepest feelings about you in writing. epidemic moreover, his lasting legacy beginning in the early You and I met in the mid-1980s at my home in days of the HIV/AIDS pandemic. 2. Promote global development of HIV/AIDS Continued on page 2 www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY Dr. Lai-Xi Wang Inducted into Johns Hopkins Society of Scholars Director’s Message, Continued from page 1 The Institute of Human Virology’s (IHV) Lai-Xi Bethesda, Maryland. The HIV/AIDS epidemic was in full and grateful for your voice in drowning over-hyped Wang, Ph.D. was inducted Wednesday, May 20, swing. We approached each other cautiously, kind of like biomedical research claims. Second, at a personal level 2009 into the Johns Hopkins Society of Scholars, fighters gauging the others style and strength. I knew of I am grateful for your invaluable service on the Institute you only as a formidable voice for patient advocacy, a among the University’s distinguished former of Human Virology’s (IHV) Board of Advisors from its “lay person” of uncanny understanding of the science of inception in 1996 until now; grateful for your wise advice postdoctoral fellows and junior or visiting faculty HIV/AIDS, a force for political change; and the creator of to me in many facets of this epidemic; grateful for the ap- from around the world. Established in 1967 these the already renown “Project Inform”. I knew you were a plication of your keen intelligence toward the search for individuals who spent part of their careers at Johns leader of what became known as activism for patients truth; and above all grateful for your friendship in a very Hopkins have gained marked distinction in their as well as for prevention of disease. I knew of you as a difficult period of my life. fields of physical, biological, medical, social or leader of a novel movement that brought direct contact I suspect that of all the non-laboratory research con- engineering sciences of in the humanities and for and sometimes arguments between the activist and tributions to the AIDS field a few activists stand at the top whom at least five years have elapsed since their last the political leadership and for the first time in medicine of the list of the contributors. No list is without you, and Hopkins affiliation. brought medical scientists face to face with patients who for me and most of us your name is the top of the top. According to the citation could effect the pace and thinking of the scientist. I knew I close this letter with a repeat of what I said in D.C. at of the induction, “Dr. Wang you were rather unique in bridging the gap because you a gathering in your honor, were chosen to be an advisor to the Institute of Medicine, explored carbohydrate antigens and it is this: if as in sports the National Academy of Sciences, and the National we had a most valu- as a target for HIV vaccine, by Institutes of Health. You were the activist, and I a scientist able player award for an synthesizing novel oligosac- and one who was embroiled in political and media individual’s overall contribu- charide clusters to mimic the phenomena far beyond his ability to grasp. These things tions to medical health and antigens on the viral envelope. initially added to my wariness of you, but by evening’s specifically for contributions This work provided important end of that summer day in Bethesda we began to know to our advances over one new insights for HIV vaccine each other. You did not lend your friendship easily. It is as of the greatest epidemics Lai-Xi Wang design, and propelled him to if one has to earn it, and not by being “fun to be with” or in history, it would not Delaney lobbying for HIV/ even by one’s intelligence. Rather, it seems to me you had be to a scientist, scientist the forefront of the anti-HIV field. He also devel- AIDS patients rights. oped a highly efficient chemoenzymatic method to have an understanding of the core or the soul, if you administrator, or political for making glycoproteins carrying defined oligo- will, of the person. leader. Instead, it would be to an activist from San Fran- Soon we came to trust each other completely. I saccharides. This opened a new avenue to rapid cisco, Martin Delaney. Your activism was central to the learned you were far more than a pioneering activist. You promotion of the science that led to our advances, and access to various homogeneous glycoproteins that were a great and essential teacher for our times. As much your educational work and administrative leadership in are essential for probing the structure and function as anyone I know you brought simplicity out of complex Project Inform led to saving of countless lives. of this class of important biological molecules, and science and unimaginable politics, and you brought the Those of us at IHV will always carry this memory. also allows an exciting new opportunity in biotech- essence of it all to those in need, namely the patient al- Finally, it was our great pleasure to honor you a few nology to permits glycoengineering of therapeutic ready infected and those in danger of becoming infected. years back with the Institute of Human Virology’s second glycoproteins, such as monoclonal antibodies, for I owe you gratitude from two different respects. First, Lifetime Achievement Award for Public Service. We want enhancing their in vivo efficacy.” as a scientist I am grateful for your persistence in pushing you now to know that every year we will have the Martin Fifteen new members were inducted this year. us to consider practical aspects of our lab research at Delaney Lecture at our meeting and that at this May’s Dr. Wang is one of the two new members elected every step; grateful that you never let us forget the suffer- very special meeting (twenty-five years since the cause by the University’s Krieger School of Arts and ing patient; grateful for your often productive and always of AIDS was shown) there will be a special lecture about provocative research questions, formulated by your close Sciences. you.* association with the epidemic; grateful for leading the cry “I am very happy for Lai-Xi,” said Dr. Robert Sincerely, for support for HIV/AIDS research funding in the earliest Gallo, Director of IHV. “He is an extraordinary and hardest years; grateful for your regular participation Bob Gallo scientist, and we at IHV have been most pleased at our annual meeting, where you invariably provoked * Delivered on May 9, 2009 by Ms. Brenda Lein and Mr. with his work and relations with colleagues. It’s all of us (scientists) to squabble less and produce more; Mark Herrington. easy to predict that Lai-Xi will continue to be one of our most exciting scientists for the future.” During the time of this prestigious induc- tions ceremony, the Society presented Dr. Wang a medallion and certificate, followed by dinner in is published quarterly. Complimentary copies are available upon request. honor of all 2009 inductees and their spouses at Discovery the home of President Daniels Nichols House, with Questions/Comments? Contact Nora Grannell, [email protected] Editor: Nora Grannell honorary degree recipients, Trustees and faculty. Writers: Brian Vastag and Nora Grannell On Thursday, May 21, 2009, the new Scholars were Design: Graphic Solutions recognized during Commencement exercises that morning. www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 2 “HIV/AIDS Remains the Number One Global Health Threat” Continued from page 1 proper medical intervention. It is important for governments and organizations from around the world to come together and combat this collective HIV/AIDS emergency.” “President Obama is fully committed to the worldwide effort to combat HIV/AIDS, and is equally committed to the effort here at home, where we are facing a serious challenge. With more than 56,000 new infections each year and more than 1.1 million people living with HIV/AIDS in the United States, we continue to have a very serious domestic epidemic. As part of the National HIV/AIDS Strategy develop- ment process, we will be developing strategies to lower HIV incidence, get all people living with HIV/AIDS into care, and address health disparities,” said Jeffrey S. Crowley, Director of the White House Office of National AIDS Policy. University of Maryland School of Medicine Dean Albert E. Reece, Crowley, Montagnier and Gallo on May 8, 2009. “Despite many advances in HIV research from the virus discovery to the antiretroviral was the cause of AIDS. This significant global in a symposium, “25 Years After Discovering therapy, the AIDS epidemic is still spreading contribution lead to the development of the HIV as the Cause of AIDS,” co-hosted by the and remains a major health problem in many HIV blood test, thereby diagnosing individu- University of Maryland School of Medicine countries,” said Dr. Montagnier. “It is therefore als and helping to control the pandemic, while and the National Cancer Institute. The sym- of utmost importance to continue the research paving the way for drug and vaccine research posium, was held May 9-11, 2009, and looked to find new ways of treatment and prevention initiated at the National Cancer Institute back at the origins of research on human for eradicating the virus infection.” (NCI). These reports followed the publication retroviruses and the 25 years since proving This global action coincided with the pub- by Dr. Montagnier and his co-workers who HIV as the cause of AIDS, summarized the lishing of Dr. Gallo and his colleagues’ four key showed the first existence of this new retrovirus accomplishments of a successful research groundbreaking articles in Science magazine, and subsequently contributed to demonstrate enterprise, and looked ahead to overcoming May 4, 1984 Vol 224 (#4648). These four its causative role in AIDS.” obstacles in treatment and prevention for the papers proved how the then-new, deadly virus Drs. Gallo and Montagnier also participated global AIDS epidemic.

Lessons Learned in Vaccine Development By Stanley A. Plotkin, M.D. (an extract from an during the 1962-63 rubella pandemic. Why was Similarly, a formalin inactivated RSV vaccine was article published in the Journal of the International it successful in giving immunity? Of course the tested in infants, many of whom developed severe AIDS Society, 2009) answer is that because neutralizing antibodies to respiratory disease after subsequent natural infec- We have recently heard many sober pronoun- rubella present in the serum and on the mucosa are tion with the virus. cements on the possibility of an HIV vaccine and correlates of protection both in preventing nasop- The pathogenetic features of these adverse re- the cancellation of what was to have been a clinical haryngeal implantation and subsequent viremia. actions were similar. In both cases the antibodies test of the prime-boost concept. There is no doubt However, things are not always that easy. Para- elicited had either disappeared or were non-pro- that the results of STEP were disappointing; but myxoviruses measles is an example. Live measles tective because they were directed against the HIV is not the only vaccine to experience diffi- virus has been a great success in eliminating the wrong protein. Although I will not argue strongly culties. So what lessons can we glean from prior disease, but in the early days there was also a that this type of reaction could also explain the pu- vaccine development? licensed, killed-measles vaccine. Unfortunately, tative enhanced acquisition of HIV in the STEP trial, First, let’s look at an uncomplicated example: antibodies induced by the killed vaccine were not it at least illustrates the idea that in the absence the rubella vaccine, one of my personal favorites. long-lasting, and when vaccinated children were of functional antibodies, cellular immunity of the This is a live attenuated virus that was isolated exposed to wild measles they suffered an atypical. Continued on page 12

www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 3 A Compelling New Mechanism for HIV Cellular Entry Grants Viruses are generally thought to enter cells by one remains visible when the virus fuses with endo- Alash’le Abimiku, PH.D., of two mechanisms: they either fuse directly with the somes. So there’s a clear-cut difference when the Research Assistant Professor, Insti- cell’s plasma membrane, or they are taken up by the virus fuses at different locations, says Melikyan. tute of Human Virology, received cell in a process called endocytosis, and fuse with After looking at thousands of viral particles, “we a one-year $268,595 National compartments called endosomes. While HIV has so saw to our surprise that real fusion or content deliv- Institutes of Health agreement far generally been considered to use the first mecha- ery, which is the surrogate of infectivity, occurs only in consortium with Vanderbilt nism, evidence for this has been mostly indirect, and in endosomes,” says Melikyan. On the cell surface, University and from the Center it is still not clear exactly how HIV infects cells. HIV seemed to undergo only partial fusion, involving for Disease Control for her work entitled, “Implementation of Recent research from IHV sheds new light on exchange of lipids and activation of fusion proteins, Alash’le the topic. The study, published in the May 1 issue but never completing the content delivery process. Abimiku Programs for Prevention, Care of the journal Cell, shows that at least in some cells The fact that the virus was unable to infect and Treatment of HIV/AIDS in the HIV needs to undergo endocytosis to deliver its through the plasma membrane led Melikyan and his Federal Republic of Nigeria Under PEPFAR.” contents into the cell. “This is important, definitive colleagues to consider the possibility that HIV might Manhattan Charurat, PH.D., work, showing that at least in require cellular co-factors Assistant Professor, Institute some cell lines HIV is primarily present in the endosomes of Human Virology, received a endocytosed,” says Dr. Robert to complete fusion. In four-year $2,867,893 National Gallo, Director of the Institute fact, when they tested Institutes of Health grant from the of Human Virology (IHV) at the dynamin, a cellular protein National Institute of Allergy and University of Maryland School normally involved in en- Infectious Diseases for his work of Medicine. docytosis, they found that entitled, “Acute HIV Infection and According to Dr. Gregory it seemed to be necessary Pregnancy.” Also on the grant are Melikyan, the IHV researcher for the virus to fuse with key personnel from IHV including Manhattan Charurat who served as senior author on endosomes and release its William Blattner – other significant the study, “we were basically contents into the cytosol. contributor, Alash’le Abimiku - co-investigator, and interested in the mechanism This sets the stage for Jean Carr –investigator. of fusion between the HIV many future experiments Wuyuan Lu, PH.D., Associate envelope and cellular mem- to try to understand the Professor, Institute of Human Virol- branes. What I realized was that cell biology that is going ogy, received a one-year $45,000 the tools were not in place to on, says Melikyan. “We grant from the CRF Program Pilot answer this question.” have to try to come up Grant competition for FY2009 for Melikyan and his colleagues with creative ways of his work entitled, “Discovery of (Kosuke Miyauchi, Yuri Kim, knocking dynamin down D-Peptide-Based p53 Activators Olga Latinovic and Vladimir and going after dynamin for Anticancer Therapy,” University Morozov) took two major ap- partners, because it may of Maryland Marlene and Stewart proaches in their study. In one, not be directly involved.” Wuyuan Lu Greenebaum Cancer Center. they optimized a technique to A drawing (right) and images (left) depict the The approaches used Gregory trap a bacterial enzyme, beta- HIV-1 entry route via endocytosis and fusion in the study are also ap- Melikyan, PH.D., Associate Profes- lactamase, inside the viral par- with an endosomal membrane. A single virus plicable to other viruses. sor, Institute of Human Virology, ticle. They could detect when co-labeled with membrane and content markers According to Melikyan, received a two-year $375,000 this enzyme was delivered into moves toward the cell nucleus and releases its “there are indications that National Institutes of Health grant the cytosol. They then used content into the cytosol. The bottom image for many viruses, depend- from the National Institute of Al- 2 inhibitors – a peptide that shows the virus trajectory. ing on cell types, there lergy and Infectious Diseases for his inhibited the fusion of the virus to the plasma mem- is a block for fusion on entry at the (cell) surface.” work entitled, “Functional Charac- brane, and a low-temperature block that inhibited all Another important step would be to repeat the ex- terization of the Hepatitis C virus fusion – to identify where the virus fused. periments in other cell lines. Melikyan also plans to E1-E2 Glycoproteins.” This funding Gregory According to Melikyan, “if all fusion events occur extend their approach to primary T-cells, the major is supported by the American Melikyan at the cell surface, no matter whether you apply the targets of HIV in human infections. Recovery and Reinvestment Act of 2009 (stimulus peptide or the low temperature you will get identical The study’s finding that HIV appears to get quickly funding). results.” What he found, however, was that viruses get endocytosed also has implications for anti-HIV Dave Pauza, PH.D., Assistant quickly taken up in endosomes, where they are pro- drugs. Gallo points out, “if this proves to be true Director, Institute of Human tected from the peptide. They then remain there, still in primary cells, treatment and vaccine research Virology, received a four-year susceptible to the low-temperature for a considerable need to be reevaluated to keep this in mind. This $1,238,776 National Institutes of time before they fuse. could lead to new approaches.” “Once the virus is Health grant from the National This was an unexpected result, and to confirm it inside, most inhibitors are not getting to the virus Cancer Institute for his work en- Melikyan and his colleagues developed their second anymore,” says Melikyan. His study suggests that titled, “Mechanisms for depleting approach, a way to directly image fusion of a single some drugs could be more potent if endocytosis was tumor immunity in AIDS.” Also viral particle. “We labeled both the envelope mem- delayed. The fact that the virus appears to spend on the grant are key persons: brane and the interior of the virus.” If the virus deliv- more time inside the cell also raises the possibility Dave Pauza Cristiana Cairo, Investigator (IHV) ers its contents into the cell, the green fluorescent of developing membrane-permeable inhibitors and Andrei Chapoval, Investigator, protein used to mark the interior of the virus escapes to target the virus in endosomes. Melikyan adds, Assistant Professor, Department of Otorhinolaryn- into the cytosol and disappears. Similarly, when the “of course if dynamin or other cellular partners are gology-Head and Neck Surgery, SOM. virus fuses to the plasma membrane, the dye present involved, then hypothetically speaking one could go on the viral envelope disappears. However, this dye after cellular targets like that to minimize infection.” www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 4 Board Buzz

Jeff Trammell Richard E. Hug Named to Joins IHV Board BankAnnapolis Board of Directors of Advisors Richard E. Hug, Chair- Environment. Additionally, Hug served on the Trammell is president and founder of Tram- man and CEO of Hug board of Maryland National Bank from 1986 to mell and Company, a public affairs consulting Enterprises, Inc and IHV 1993. firm in Washington, D.C. Previously Trammell Board of Advisor member Hug is a 1956/1957 graduate of Duke Univer- served as Senior Managing Director of Hill & was elected last month to sity and began his business career with Koppers the Board of Directors of Company, Inc., where he was named a corpo- Knowlton, an international public affairs/com- BankAnnapolis, a firm rate vice president in 1973. In 1983, he became munications firm, from 1988 to 2000, where he specializing in business and President, Chairman and Chief Executive oversaw the firm’s public affairs practice. He was real estate investment and Officer of Environmental Elements Corpora- a senior advisor to Vice President Al Gore dur- consulting. tion, a firm specializing in air pollution control ing the 2000 presidential campaign and headed Dick Hug Hug is well known for his systems for the utility and industrial markets. business outreach for the Gore campaign, as well civic involvement and has After a successful IPO in 1990, the company as serving as liaison for con- served as chairman of the Maryland Chamber was listed on the New York Stock Exchange in stituent groups. Trammell of Commerce, Maryland Business for Respon- 1991. Hug retired in 1995, but remained a direc- served in a similar capacity sive Government, Leadership Maryland, The tor, stockholder, and Chairman Emeritus until for the Kerry 2004 presiden- National Aquarium in Baltimore, the Kennedy the company’s sale in 2006. tial campaign. Krieger Institute, the United Way of Central Hug, 74, resides in Arnold with his wife Lois. Maryland and the Duke University School of the Trammell worked for a They have two children and four grandchildren. number of years in the U.S. Senate and the U.S. House of Representatives, where Judge Arthur Gajarsa Receives Prestigious he was counsel to the chair Jeff Trammell of the Subcommittee on Health and Environment of the House Commit- Sons of Italy Foundation Honor tee on Energy and Commerce. He founded a IHV Board Member, the successful publishing company which produced Honorable Arthur J. Gajarsa, annual references on Congress and government federal judge for the U.S. organizations. Court of Appeals, was one Trammell serves on several boards, including of three honorees during the the Board of Visitors of the College of William Sons of Italy Foundation’s and Mary, where he is a member of the executive (SIF) 21st annual National Education & Leadership committee. Trammell was the founding chair of Awards (NELA) award cer- the Board of the Thomas Jefferson Public Policy emony. While Gajarsa was Program at William and Mary and continues as honored with the 2009 SIF a member of that board. He has served on the Lifetime Achievement Award board of the Human Rights Campaign, the Gay in Jurisprudence and Italian and Lesbian Victory Fund, which he chaired, and American Leadership, U.S. the U.S. Holocaust Memorial Museum advi- Vice President Joseph R. Biden sory board for remembrance of gay and lesbian was presented the NELA victims. award as the first person not of Gajarsa receiving his award during the Sons of Italy Foundation’s 21st an- He holds a B.A. in American History from Italian heritage but a longtime nual National Education & Leadership Awards (NELA) ceremony. Photo William and Mary and a J.D. from Florida State friend of Italian Americans. by Max Taylor. University. www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 5 Honoring Robert C. Gallo, MD for Historic Contributions to the Science of HIV and AIDS

Gallo and Townsend greeting the Honorable Shirley Nathan-Pulliam, Maryland State Delegate and Maryland House Majority Whip, during a By Larry Roberts, University of Maryland, School of Medicine reception before the Gala.

May 4, 2009 was the 25th anniversary be able to recognize Dr. Gallo for this transformative forging a greater understand- of Dr. Robert Gallo and his coworkers four Science magazine achievement.” ing of differences in sexuality, publications identifying HIV as the cause of AIDS, widely The symposium - “25 Years After Discovering HIV women’s rights, and uniting recognized as one of the most important scientific discoveries as the Cause of AIDS” - reviewed the past, present powerful governments with in history. Dr. Gallo, the director of the Institute of Human and future of HIV research, treatment and education. third world countries.” Virology at the University of Maryland School of Medicine, Co-hosted by the School of Medicine and the National Dr. Gallo was recognized and his colleagues proved HIV is the cause of AIDS by isolating Cancer Institute (NCI), the symposium provided an for his pioneering research and cultivating the retrovirus from many patients with AIDS. opportunity to recognize the contributions of scien- achievements in a special Dr. Gallo also led the team that developed the blood test for tists from a wide range of disciplines. Dr. Gallo said gala. Celebrating a Visionary’s AIDS, saving countless lives by preventing new infections. The the symposium, held at the Marriott at Camden Yards, Quest for Discovery: An blood test (for antibodies to HIV) was also another important inspired young scientists by documenting progress in Evening Honoring Dr. Robert component that linked HIV to AIDS. AIDS research. “The role of scientists at the NCI in the C. Gallo, MD, was held May To commemorate Dr. Gallo’s historic discoveries, the Univer- co-discovery of HIV, the development of the HIV blood 9th at the Baltimore Hilton. sity of Maryland School of Medicine hosted a special scientific test and the beginning of anti-retroviral drugs should The gala brought together symposium and gala, “Celebrating a Visionary’s Quest for not be forgotten.” colleagues, friends, family and Discovery” held May 9-11 in Baltimore, Maryland. Dr. Gallo’s Over the last quarter of a century, AIDS research has the public to thank Dr. Gallo discovery is shared with Luc Montagnier of the Pasteur Institute eased the suffering caused by the disease and given birth The Honorable Kathleen Kennedy Townsend, for his historic contributions to the field of modern human immunology. Dr. Gallo IHV Board of Advisor Chair, emceed the Gala to AIDS research and his in France, who also attended the events. program. “The co-discovery is one of the seminal events not only in says around the world, the fight against AIDS has led to continuing dedication to find- HIV research but in our understanding of how retroviruses in unprecedented cooperation and coordination among commu- ing a vaccine. The master of ceremonies was former Maryland general cause disease and how they might be thwarted,” says nity leaders, patients, advocates, physicians, scientists and poli- Lt. Governor Kathleen Kennedy Townsend, who chairs the Dean E. Albert Reece, MD, PhD, MBA. “We are honored to ticians. “AIDS research also had a spin-off affect on society by Institute of Human Virology Board of Advisors.

www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 6 One of seven Gallo “roasters” the evening of May 9, 2009, Dr. National Institute of Allergies and Infectious Diseases Robert Anthony is Gallo’s cousin and close confidante and Director Tony Fauci addressing the audience during the Chief of Cardiology at St. Mary’s Hospital in their hometown symposium. of Waterbury, CT. Other roasters included Dr. John Ger- shoni, Professor of Cell Research and Immunology at Tel Aviv University; Dr. Max Essex, Chairman of the Harvard School of Public Health AIDS Initiative; Dr. Isaac Witz, Profes- sor Emeritus of Cell Research and Immunology at Tel Aviv University; Dr. Bill Blattner, Associate Director of the IHV; Tim Moynahan, Esquire, Chairman of the Robert C. Gallo Foundation for AIDS & Virus Research and Mr. Stewart Greenebaum, member of the IHV Board of Advisors.

Dr. Bernadine Healy, U.S. News and World Report Gallo and Townsend greeting the Honorable Shirley Nathan-Pulliam, Maryland State Delegate and Maryland House Majority Whip, during a reporter and former Director of the National Institutes of reception before the Gala. Health making opening remarks at the symposium.

forging a greater understand- ing of differences in sexuality, women’s rights, and uniting powerful governments with third world countries.” Dr. Gallo was recognized University of Maryland School of Medicine Dean Albert E. for his pioneering research Reece presented Gallo with a gift of a Brooks Robinson auto- graphed 1966 Baltimore Orioles jersey. achievements in a special National Cancer Institute Director John Niederhuber mak- gala. Celebrating a Visionary’s ing introductory remarks during the symposium. Quest for Discovery: An Evening Honoring Dr. Robert C. Gallo, MD, was held May 9th at the Baltimore Hilton. The gala brought together colleagues, friends, family and the public to thank Dr. Gallo The Honorable Kathleen Kennedy Townsend, for his historic contributions IHV Board of Advisor Chair, emceed the Gala to AIDS research and his program. continuing dedication to find- Gallo and Dr. Anders Vahlne, Professor of Clinical ing a vaccine. The master of ceremonies was former Maryland Drs. Max Essex, Chair of the Harvard AIDS Initiative and Virology at the Karolinska Institute, who spoke during Lt. Governor Kathleen Kennedy Townsend, who chairs the IHV Scientific Advisory Board Member, Gallo and Bill the symposium about the history of retroviruses and Haseltine, Chairman and CEO of Haseltine Associates, Ltd., recently published in May 2009 an article in Retrovirol- Institute of Human Virology Board of Advisors. President of the William A. Haseltine Foundation for Medical ogy entitled, “A Historical Reflection on the Discovery of Sciences and the Arts and IHV Board of Advisor Member. Human Retroviruses.”

www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 7 IHV – Providing Aids Relief Services Worldwide Through the President’s nurses, adherence specialists, lab- Emergency Plan for AIDS Relief oratory technicians and commu- (PEPFAR) funding, the Institute nities in resource limited settings of Human Virology (IHV) of the in Africa and the Caribbean. University of Maryland School IHV SOM is responsible for the of Medicine (SOM) is having an medical and clinical outcomes enormous, global impact on those of AIDSRelief including clinical suffering from HIV and AIDS. capacity building, AIDSRelief’s Catholic Relief Services partners medical curriculum, quality with IHV SOM, Catholic Medical assurance and quality improve- Mission Board, Interchurch Medi- ment in addition to laboratory cal Assistance and Futures Group procurement, installation and to collectively form AIDSRelief training. IHV SOM physicians Consortium. In 2004, AIDSRe- work closely with local partners lief was awarded a competitive for drug regimen supply chain five-year PEPFAR grant from the management through evidenced U.S. Health and Human Services based forecasting and regimen (HHS) to provide HIV care and Dr. Robert Redfield greeting children in Africa selection. antiretroviral therapy (ART) in The goal of IHV SOM AID- the following nine countries: South Africa, Zam- Robert Gallo, Director of IHV and Professor of SRelief is to provide care and treatment for HIV bia, Nigeria, Kenya, Rwanda, Uganda, Tanzania, Medicine and Microbiology and Immunology at patients and their families through supportive Haiti, and Guyana. AIDSRelief is one of two ma- the School of Medicine. “AIDSRelief’s significant care delivery models which are sustainable and jor PEPFAR grants IHV SOM implements and is contributions, including care and therapies for which can be replicated or scaled-up relatively led by Dr. Robert Redfield, Co-Director of IHV more than 350,000 HIV-positive Africans and easily. A program implemented successfully and Professor of Medicine, and Microbiology Caribbeans, are historical legacies for IHV and through IHV SOM in Baltimore known as the and Immunology at the School of Medicine. the School of Medicine.” JACQUES Initiative has served as a model for At the close of year five of the grant, AIDSRe- AIDSReleif strives to achieve durable viral IHV SOM’s programs in Africa and the Carib- leif is proud to reflect on its accomplishments suppression through first line regimens. Pro- bean. IHV SOM has been successful both locally in “Providing Treatment and Restoring Hope,” grams that demonstrate durable therapeutic and now globally in developing and building the program’s mantra. It has made remarkable outcomes are more cost-effective over the long upon the JACQUES Initiative’s programs that progress improving the quality of life for people run, as fewer patients require more expensive has translated a non-traditional model of care living with HIV around the world, while scaling second-line and salvage regimens or costly diag- energizing people living with HIV into an effec- up access to services. Most importantly, this nostic testing. Maintaining maximum HIV viral tive community-based health delivery system. work has been conducted in a context which suppression is the basic treatment goal of ART This scalable model, which is not limited to the supports country programs’ National Treat- upon which all other outcomes rest – including traditional healthcare workforce, includes ART ment Plans and strengthens and empowers local immune restoration, decreased morbidity attrib- adherence and treatment support using people healthcare systems. As of November 30, 2008, uted to opportunistic infections, AIDS-related living with HIV infection as treatment guardians AIDSRelief is providing 141,669 patients with mortality, quality of life, and long-term costs of and treatment specialists to form a strong and ART and has enrolled 382,189 patients in HIV care. Results from AIDSRelief’s second-round expanded community of health network. care and treatment at 187 local partner treatment patient-level outcomes indicate high levels of “on As AIDSRelief enters the sixth year of opera- facilities in the aforementioned nine African and treatment” viral suppression including Kenya at tions under the newly reauthorized Lantos-Hyde Caribbean nations. AIDSRelief’s strong focus on 94.6%, Zambia at 92.4%, Nigeria at 86.2% and Act of 2009, the program will continue building a comprehensive continuum of care from health Rwanda at 89.3%. local capacity with the goal of preparing and institution to community and household has “I have been enormously privileged to work graduating local partners who are ready to oper- continued to demonstrate a low level of patients with an outstanding group of deeply committed ate independently. IHV SOM continues to play a lost to follow-up care at 5.33%, while cumulative health professionals to share the experience and critical role in medical education and curriculum mortality remains around 8.1%. Recently this capacity of IHV SOM globally and contribute development to a cadre of highly trained group grant was renewed through 2013. to the impact and success of our nation’s global of local doctors, nurses, community health work- “Dr. Redfield’s program has been extremely health programs,” said Dr. Redfield. ers, laboratorial specialists and other healthcare successful in assisting these PEPFAR countries IHV SOM’s role in the Consortium is to professionals to optimize sustainable health in therapy, education and training,” said Dr. impart years of work in HIV/AIDS to physicians, intervention. www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 8 Vigil Focuses Attention on HIV/AIDS Impact

and Kim Weingarten-who organized both the first HIV Over Fifty conference at Johns Hopkins course and the vigil. University in 2002 and who volunteers services to “The success of the evening was not only improve the lives of African-Americans; Debbie about the number of people who showed up for Rock, MSW, the founder and executive director of the vigil, but who signed up to volunteer with the LIGHT Health and Wellness Comprehensive our Initiative and who agreed to get tested,” said Services, Inc., which serves families and children Derek Spencer, MS, CRNP, executive direc- impacted by health and social issues such as HIV/ tor of the JACQUES Initiative. “Additionally, I AIDS and substance abuse; and the Rev. Debra want to thank IHV’s Board of Advisor Member Hickman, MDiv, co-founder, president, and CEO Fred Cannon, Senior Vice President of BMI, for of Sisters Together and Reaching Inc. (STAR), a helping to enlist The Marcus Johnson Project’s faith-based, nonprofit organization that provides support for entertainment during the event.” spiritual support, direct services, and prevention Nearly 200 people from across the city gath- education to HIV/AIDS infected and affected men ered on campus for the event, including Delta and women. Psi Theta Sorority Sisters, students from Roland Wasserman was also honored for her work Park Country School and Steuart Hill Academic conceptualizing and organizing the vigil due to Academy, leaders from the city’s faith commu- her passion for raising awareness about the virus nities, government officials, front-line health on campus. care workers, HIV/AIDS patients, and medical Angela Wakhweya, MD, MSs, deputy director researchers. of the Maryland AIDS Administration, discussed “Having awareness without being engaged is the epidemiology of the virus’ impact on women criminal. We want to raise awareness and engage and girls, saying that everyone must embrace the Candlelight by Antonio Paterniti people. We want to help people become engaged triple Ts: Talk, Testing, and Treatment. in dealing with the problem, a call to action,” “We must talk consistently and constantly about By: Rosia Scalia, University of Maryland, Baltimore Spencer said. where we are with the epidemic,” Wakhweya said. It started with a candlelight vigil to raise Three women who serve on the front lines “We must urge people to be tested, at least once awareness about the devastating impact of the of HIV/AIDS treatment were honored: Dorcas a year and twice a year if they are at risk, and we HIV/AIDS epidemic on women and girls. It ended Baker, RN, BSN, ACRN, MA, who organized the must be able to treat early, before AIDS sets in.” with the shocking news that a volunteer who took the rapid test that evening screened positive for the virus. Staff at the JACQUES Initiative, part of the University of Maryland School of Medicine’s Institute of Human Virology (IHV), will treat her. Named in honor of a patient advocate who espoused education, research, and informed deci- sion making, the JACQUES Initiative monitors prescription medication and provides drug addic- tion counseling, help with housing, insurance, job search training, and the like. The vigil-a community event associated with the interdisciplinary course Women: The Changing Face of HIV/AIDS-was organized by six Master’s of Social Work degree students and their two Maternal and Child Health (MCH) doctoral fellow advisors. “Through their efforts, these women have brought our campus together with the community, illuminating how HIV/AIDS impacts women throughout our community, state, nation, and world,” said Edward Pecukonis, PhD, MSW, an associate professor at the School of Social Work who directs the School’s Maternal and Child Health educational program. Doctoral students Shauna Acquavita, LCSW-C, BCD, and Maya Gibbons, MSW, provided guidance to the six MCH scholars-Kerri Agee, Caitlin Johnson, Erin Penniston, Jessica Porto, Kate Wasserman, Members of the public participate in IHV’s free HIV testing during the event. Photo by Antonio Paterniti. www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 9 Longtime Gallo Colleague Popovic Enters Semi-Retirement Memory B Cells In 1973, the universe of retrovirus National Cancer Institute Director Sam Broder and his co-workers. researchers was small, and those The blood test became available by February 1984 in the Gallo interested in the possibility of hu- lab, and its application was made available to industrialized coun- Reveal Early man retroviruses were really very tries through larger companies – first by Abbott and later others. small. So when two of them, Robert During that critical work with HIV, in 1983, Popovic was grant- Response to HIV Gallo and Mika Popovic, collided at a ed political asylum in the U.S. When he arrived in the U.S. in 1979, Natural HIV suppressors – people cancer meeting in Oslo they did what he had planned to return to Czechoslovakia after a few years. “I who contract HIV but whose immune was natural – they gabbed about was already established over in Czechoslovakia, I was head of the systems control the infection – often their mutual interest at a pub. “It was department,” he says. But political turmoil in Czechoslovakia – the have low levels of anti-HIV antibod- mid-summer, one of the longest days Soviet Union still had sway at that time – left Popovic with few of the year, and at 10 p.m. it was nice choices. So he stayed in the U.S., not returning to his homeland ies in their blood. That finding has Mika Popovic and warm and there was sunshine, until after the Berlin Wall fell – the first of several visits since. puzzled researchers. New research led and we were outside drinking beer He joined IHV at its inception in 1996, and has continued con- by IHV’s Co-Director of Division of and talking about retroviruses,” remembers Popovic, who is tributing to the understanding of HIV and other retroviruses. In Basic Science and Vaccine Research, semi-retiring from his position as Professor at IHV. “I was looking particular, he’s helped explain why lymphomas occur frequently George Lewis, concludes that such for some evidence that a human retrovirus can be involved with in HIV-infected individuals. various cancers, and Bob Gallo was interested in the same thing. Although Popovic is semi-retired, he still has his hands in individuals That was our first contact.” three projects. First, he is looking for retroviruses in lung cancers did, at some At the time Popovic was a post-doctoral fellow in a cancer lab that form in non-smokers. His second ongoing project involves point, generate in Sweden. A few years earlier he had finished an M.D. in his native searching for HIV proteins in the blood of patients taking highly antibodies that Czechoslovakia, but after a year working at a hospital Popovic active retroviral therapy. “The work is not finished but it looks like, targeted HIV. decided to pursue a research career instead. So he enrolled in a yes, the patients do have circulating viral proteins” even though Ph.D. program and met his mentor, Jan Svoboda, a noted Czech they have no detectable viral RNA in their blood, Popovic says. “My hunch virologist with a keen interest in avian (chicken) retroviruses. For the third project, Popovic is collaborating with researchers in is, the antibod- Popovic adopted that interest, and ran with it. Michigan, Sweden and Germany to search for microbial agents ies we found do George Lewis In 1979, that interest paid off when Gallo invited Popovic to that might trigger sarcoidosis and other diseases characterized contribute to work in his lab at the National Cancer Institute. By 1980 Gallo by granulomas. control of HIV in these individuals, and his co-workers had discovered and isolated the human T cell To keep up his lab work, Popovic draws inspiration from his leukemia lymphotropic virus 1 (HTLV-1), the first known human former mentor, whom he visited recently in Prague. At 75, Jan but they’re probably not the whole retrovirus. Then Popovic, Gallo et al. plus independent workers Svoboda still spends time in the laboratory, writes, and publishes story,” said Lewis. The research was in Japan, showed it was the cause of adult T cell leukemia. Later his research. “If he can work so actively at 75, I should still work at published in the March 10 Proceedings it was shown by Antoine Gessaine and Guy de Thé of France to 68,” says Popovic. of the National Academy of Sciences. cause a fatal neurological disease as well. “He joined us after we When he’s not working, Popovic plans to garden, fish, and read Three natural viral suppressors who discovered HTLV-1, and Mika did a marvelous job on the next books on history, a favorite subject. step of that work, the biological part,” says Gallo. Specifically, “In late 1970, the field of human retrovirology as an area of had been infected with HIV for 5, Popovic along with Isao Miyoshi in Japan showed that the virus research was thought to be maintained only by a ‘political skill’ of 13, and 17 years were studied. None transformed certain immune cells (CD4 T cells), immortalizing a few researchers and human retroviruses were termed as ‘human of the volunteers had ever received them (ie the cells grew forever). He also obtained many more rumor’ viruses,” said Popovic. “However, it is very difficult to anti-retroviral therapy, yet their blood isolates of HTLV-1. imagine that in early 1980’s the field of human retrovirology could levels of HIV remained very low. Popovic’s next major contribution arrived in 1984, as co-author have been developed so rapidly without Bob Gallo’s outstand- on four Science papers that outlined HIV as the cause of AIDS. ing knowledge and expertise in the field as well as without his Lewis and his colleagues (Yongjun Popovic was the lead author on one of the papers, which de- extraordinary capacity and skill to maintain a well supported Guan, Mohammad M. Sajadi, Roberta scribed how to culture HIV and grow large amounts of it, a critical Laboratory of Tumor Cell Biology (NCI) with outstanding research- Kamin-Lewis, Timothy R. Fouts, An- step in developing reagents to test the blood supply for HIV, a key ers working in this field in a highly competitive NIH environment. thony Dimitrov, Zhixin Zhang, Rob- concern at the time. One should take in consideration that in 1982, when the AIDS ert R. Redfield, Anthony L. DeVico “My main contribution was that I succeeded in showing that epidemic started in this country, vast majority of retrovirolo- HIV could be isolated and grown in sufficient amounts in cell gists moved into other areas of research, mainly into the field of and Robert C. Gallo) found that the lines,” says Popovic. oncogenes, and the NIAID laboratory for retroviruses was focused three volunteers also carried very low Gallo says the paper “was a technical breakthrough that made on studies of human endogenous retroviral sequences instead of concentrations of anti-HIV antibodies the development of the blood test quite rapid and easy. It was a exogenous retroviruses. Without discussions, at the beginning of in their blood. “We knew that sup- major advance. Mika is the first author because as Gallo notes “his the AIDS epidemic, the best prepared laboratory to face this new pressors already made antibodies to along with my technicians were the hands that were wet. It took epidemic and find effective solutions was Bob Gallo’s laboratory.” a lot of experimentation to get that to succeed.” Gallo points out “During my work in Bob Gallo’s laboratory which encompasses the envelope protein because they had that the blood test was not only essential for saving the blood almost three decades, I faced with Bob Gallo ‘good time’ and ‘bad low levels of them in the circulation. supply and protecting people in need of donor blood from being time,’” continued Popovic. “A reporter, Malcolm Gladwell, who So we researched the memory pool to infected with HIV contaminated blood, its use also became a covered science and medicine for The Washington Post magazine find specificities that were not in the major factor in showing HIV was the cause of AIDS. Further, by described my work with Bob Gallo as follows: In retrospect, it was serum.” said Lewis. knowing people were infected long before they developed AIDS, the purest of good fortune that a year before the AIDS retrovirus education of infected people could begin, and when treatment surfaced in the West, these two men [Bob Gallo and Mika Popovic] “Memory B cells are just what you’d became available, physicians could know who to treat years in ad- with their passionate, shared interest in this obscure field linked up at expect,” said IHV Director Robert vance of clinical signs of AIDS. In addition, the cell culture system the world’s most important research institution. When others around Gallo. “They’re like a library of the enabled scientists to test drugs against HIV and so contributed the world were looking for fungi or bacteria or chemicals as the cause pathogens we’ve previously been to the pioneering work of anti-HIV drug development by former of AIDS… ,” Popovic recalled. Continued on page 11 www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 10 From Bad Fall, to Great Spring Memory B Cells Reveal Last fall and the early days Early Response to HIV, of the New Year were challeng- Continued from page 10 ing ones for IHV’s Director, Dr. Robert C. Gallo. It began with exposed to.” the “un-noble Nobel” decision as Each memory B cell produces antibodies reported in the press, included against a single target, and after an infection a battle in South Africa with clears, memory B cells lie in wait. And they can typhoid fever and ended in his wait a long time. A paper published in Nature good friend, Marty Delaney’s last year found memory B cells specific for passing. the 1918 flu in nonagenarian survivors of that However, this past spring was pandemic. Antibodies generated by those B quite another story. On March cells neutralized the 1918 virus. 12, Gallo received the Governor’s Lewis wanted to know if antibodies gener- International Leadership Award, ated by the natural HIV suppressors were the most esteemed international Evening of the Dan David Prize ceremony on May 17, 2009. From right to left: capable of neutralizing the virus. “We’d like to First row: Prof. Andrew E. Lange, Prof Paul Richards, Prof. Robert C. Gallo, award bestowed by Mary- Mr. Ron Huldai Mayor City of Tel Aviv-Jaffa , Prof. Zvi Galil President Tel Aviv know what the specificity of B cells are. These land, recognizing decades of University, Mr. Gianni Alemanno Mayor of Rome, Mr. Dan David, Prof. Paolo are people who are controlling infection and sustained and exemplary global de Bernardis, Prof. Dani Leviatan Rector Tel Aviv University. Sitting: Mr. Shimon we think they made some antibody responses Peres President of the State of Israel, Mr. Tony Blair. Standing in front: Mrs. Gabi leadership of those providing a David. early on that have smoldered down because significant positive impact on The Honorable Antonio Bassolino. Gallo received this there isn’t a [viral] load,” said Lewis. Maryland and its global footprint. “I am privileged to Medal on April 16 for “his discovery and pioneering So after isolating the HIV-specific memory honor Dr. Gallo and the Institute for Human Virol- fundamental studies on human retroviruses and their B cells from the three volunteers, the team de- ogy for their dedication in resolving some of the role in oncology and immunodeficiency.” termined what part of the virus they targeted. most challenging medical problems facing people Gallo was in New York to receive an Honorary “Some of the monoclonal antibodies we’ve iso- worldwide, and helping to find a vaccine that can Doctor of Science at Mount Sinai School of Medicine’s lated look interesting, and we can now transfer help thousands of people affected by the HIV/AIDS Commencement on May 14. He then flew directly them into animals and see if they block model epidemic,” said Governor Martin O’Malley. to Tel Aviv, Israel where he was presented on May 17 HIV viruses from infecting the animals,” said On March 26, Gallo was in Ocho Rios, Jamaica to with the international Dan David Prize, named after Lewis. receive two awards including an honorary degree of global businessman and philanthropist Dan David. The antibodies Lewis and his colleagues doctor of science from the University of Technology Annually, the Dan David Prize awards three prizes of recovered from the memory B cells of the three (UTech), and the Sir Allister McIntyre Distinguished US$1 million each for outstanding achievement and volunteers attack various sites on the HIV en- Award from the University of West Indies (UWI’s) in turn, the laureates donate 10% of their prize money velope protein. Some block the HIV co-recep- University Diabetes Outreach Programme. towards 20 doctoral and postdoctoral scholarships. tor, where HIV locks onto CD4 immune cells On April 14, Gallo was in The Dan David Prize chooses after binding with them. Ireland to receive the James The week in Israel with my winners “in the Past, Present and However, he added that it’s impossible to Joyce award from the Liter- “family and friends, was the Future Time Dimensions.” Gallo know how many of these antibodies the 3 ary and Historical Society at best week of my life. was chosen in the Future Dimension individuals had made in the past. The experi- the University College Dub- ROBERT GALLO “for his research of the HIV and T ments do show conclusively, though, that the lin for his role “in identifying ” cell leukemia viruses and especially volunteers did make antibodies that targeted the Human Immunodeficiency Virus as the infectious for the development of a robust, simple blood test the HIV envelope protein. agent responsible for AIDS.” The Society further to detect the HIV virus, the importance of which for “It’s a very important piece of work,” said noted Dr. Gallo’s team “worked to grow the virus in an the epidemiology of this huge pandemic cannot Gallo. He points to vaccine trials where re- immortalized cell line leading to his development of be overestimated.” Fellow recipients included Past searchers failed to find anti-envelope antibod- a blood test for HIV and the ability to screen donated Dimension winners Paolo de Bernardis (University ies in the blood of the volunteers. It may be blood for this virus.” Gallo was the first scientist to La Sapienza, Rome, Italy), Andrew Lange (Caltech, that those volunteers generated such antibod- receive this prestigious award. Past years diverse USA) and Paul Richards (UC Berkeley, USA) for their ies, but that the antibodies quickly vanished recipients have included Nobel laureates FW DeKlerk, research and data presented in 2000 which provided from the blood. “You may see a negative anti- John Hume and Seamus Heaney as well as Noam the first undisputed evidence that the Universe has a body result, when in fact the antibodies were Chomsky, JK Rowling and last year, Will Ferrell. flat geometry and Present Dimension winner former very important for controlling the disease early After his trip to Ireland, Gallo traveled directly Prime Minister of Great Britain Tony Blair for inter- on,” said Gallo. “In that way, this study helps to Naples, Italy where he was presented The Public national leadership in engineering agreements and indirectly with vaccine development.” Health Medal Award by the Governor of Campania, forging lasting solutions to areas in conflict. www.ihv.org DISCOVERY A NEWSLETTER OF THE INSTITUTE OF HUMAN VIROLOGY 11 The Institute of Human Virology (IHV) at the University of Maryland School of Medicine is a world-class center of excellence focusing on chronic viral diseases, most notably HIV/AIDS, and virally linked cancers. IHV is dedicated to fundamental and clinical research leading to improved treatment and prevention of these diseases. Our unique structure connects cohesive, multidisciplinary research and clinical programs to streamline new treatments from discovery to patient. IHV serves the global scientific community and treats patients at clinics in Maryland, across Africa and in the Caribbean.

Lessons Learned in Vaccine Development Continued from page 3 wrong type can enhance--rather than diminish-- immunity in controlling disease after infection. implantation within several days, effector B cells susceptibility. The last agent I would like to discuss is hepatitis must be in the circulation and producing antibody Another type of contretemps occurred with the C, because there are many similarities between it at the time of exposure. Thus, booster doses of an first licensed rotavirus vaccine. Although protec- and HIV. Although Hep C is a flavivirus, it shares AIDS vaccine will be necessary to maintain protec- tive, it caused intussusception (intestinal invagi- a number of properties with HIV. Interestingly, tive levels of antibody. Indeed, booster doses are nation) in some patients. This happened because patients who resolve acute Hep C infections have commonly needed for vaccines, even for some that the supposedly attenuated simian vector retained higher levels of neutralizing antibodies early in are highly efficacious. pathogenicity for the infant intestine, causing infection than do those who go on to chronic This may be an inconvenient truth, but the use diarrhea and fever. The point is that the choice infection. Antibodies do not help when they de- of adjuvants might also help. The new adjuvants of a supposedly attenuated vector is a key issue, velop late in chronic infection. On the other hand, now available in vaccinology are legion and they and that the wrong choice of vector brings safety cellular immunity developing late in infection does increase breadth as well as height of antibody problems. stop chronic viremia. Although a crucial difference responses. Another lesson is that correlates of immuni- between the two viruses is the lack of integration The lessons of vaccinology that are likely to ty may be complex, and antibody and cellular by Hep C in contrast to HIV, nevertheless I think it apply to HIV are that antibody and effector cells on immunity are often collaborative. This point can is instructive to see that a chronic infection can be the mucosa are needed to prevent implantation, be illustrated with reference to cytomegalovirus. counteracted by standard immune responses. that high levels of antibody are required to prevent As in HIV, super infection may occur in previously So what can be said about immune protection or modulate viremia, and that both CD4 and CD8 infected individuals, but the course of secondary against HIV? In general, innate immune responses cells are needed to kill cells once they are infected. infection is much less pathogenic than in non- are clearly valuable both immediately after infecti- immune subjects. Antibody to CMV alone may on and as adjuvants to adaptive immune respon- protect against primary infection, but if infection ses. The question is do they have memory? occurs, cellular immunity is critical in controlling it. I doubt that we can escape totally from having Nevertheless, two vaccines in development have to make multivalent or regional HIV vaccines. shown moderate ability to prevent or modify CMV Indeed, recent reports suggest that multivalent HIV infection. Thus, the fact that super infection has envelopes give broad neutralizing responses. IHV thanks sanofi pasteur for its been demonstrated in some already HIV infected If high levels of antibody are necessary for people does not necessarily rule out a role for protection, and as HIV spreads from the site of continued support of Discovery

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