deciphering AIDS vaccines — a Deciphering AIDS Vaccines an anthology of VAX and IAVI Report articles explaining key concepts in aids vaccine research and clinical trials VAX and IAVI Report anthology For free subscriptions to IAVI Report and VAX, please visit www.iavireport.org or email [email protected] Deciphering AIDS Vaccines fter 25 years of battling the AIDS pandemic New technologies to prevent HIV transmission Athat has already claimed the lives of more remain an imperative and an AIDS vaccine offers than 25 million people, the need for an AIDS vac- the greatest hope of all for reversing the pandemic. cine has never been greater. Last year marked the There are still many scientific obstacles to the culmination of the most ambitious global pro- development of an effective vaccine, but impor- gram to date aimed at providing antiretrovirals tant advancements have been made. Researchers (ARVs) to people with AIDS in developing coun- now have a clearer understanding of the earliest tries. Although the World Health Organization’s immunologic events in HIV infection and are ‘3 by 5’ program fell short of its target to place 3 actively studying long-term nonprogressors to million HIV-infected people on these life-saving understand the mechanisms that allow some indi- medications by the end of 2005, the funding viduals to effectively control their HIV infection from this program and others—including the without ARVs. They are also gathering new Global Fund to Fight AIDS, Tuberculosis and insights on how to manipulate animal models to Malaria and the President’s Emergency Plan for enhance the pre-clinical evaluation of vaccine can- AIDS Relief (PEPFAR)—have helped provide didates. These advancements, as well as the results ARVs to 20% of individuals in need in low- and from around 30 ongoing clinical trials of preven- middle-income countries. tive AIDS vaccine candidates in more than a This is a significant accomplishment and the dozen countries around the world, will provide momentum it has created is helping to bring researchers with important clues on how to reach hope to many communities devastated by the ultimate goal—an effective AIDS vaccine. HIV/AIDS. Importantly, these programs are also The articles in Deciphering AIDS Vaccines encouraging more and more people to be tested originally appeared in VAX and IAVI Report, the for HIV infection. But the pandemic shows little only comprehensive publications on the AIDS sign of abating. There are now about 40 million vaccine field. We hope that you enjoy and learn people infected with HIV around the globe, and from the articles in this anthology and that you 4 million of them were infected just last year. The will be intrigued to find out more. Visit soaring costs of treatment may soon make it www.iavireport.org for more information. unfeasible, perhaps impossible, to provide treat- ment to all in need. The IAVI Report Team Imagine a world without AIDS Editor Simon Noble, PhD FREE SUBSCRIPTIONS: To obtain a FREE subscription to IAVI Report and VAX, or for reprint Science Writer permission, please send a request, including full postal address, to Kristen Jill Kresge [email protected]. If you would like to receive multiple print copies of IAVI Report and VAX to distribute and/or use in your programs, please Production Manager send your request, including number of copies and postal address, to Nicole Sender [email protected]. Graphic Artist For more information, go to www.iavireport.org. Samuel Velasco [email protected] All rights reserved ©2006 The International AIDS Vaccine Initiative (IAVI) is a global not-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vac- cines for use throughout the world. Founded in 1996 and operational in 23 countries, IAVI and its network of collaborators research and develop vaccine candidates. IAVI’s financial and in-kind supporters include the Alfred P. Sloan Foundation, the Bill & Melinda Gates Foundation, The John D. Evans Foundation, The New York Community Trust, The Rockefeller Foundation, The Starr Foundation; the Governments of the Basque Country, Canada, Denmark, European Union, Ireland, The Netherlands, Norway, Sweden, United Kingdom, and United States; multilateral organizations such as The World Bank; corporate donors including BD (Becton, Dickinson & Co.), Continental Airlines, Google Inc., Merck & Co., Inc. and Pfizer Inc; leading AIDS charities such as Broadway Cares/Equity Fights AIDS, Crusaid, Deutsche AIDS-Stiftung, and Until There’s A Cure Foundation; other private donors such as The Haas Trusts; and many generous individuals from around the world. For more information, see www.iavi.org. www.iavireport.org Table of contents Understanding… the science of AIDS vaccines …the early stages of HIV infection ..................................................................................5 …mucosal immunity ........................................................................................................8 …AIDS vaccine pre-clinical development ......................................................................10 …pre-existing immunity ................................................................................................12 …long-term nonprogressors ..........................................................................................14 …HIV clades ....................................................................................................................16 An interview with… José Esparza ......................................................................................18 Understanding… AIDS vaccine clinical trials …the benefits and risks of participating in clinical research ........................................23 …community advisory boards ........................................................................................25 …capacity building at vaccine trial sites ........................................................................27 …informed consent ........................................................................................................29 …research voluntary counseling and testing ................................................................31 …couples voluntary counseling and testing ..................................................................33 …home-based voluntary counseling and testing ..........................................................35 …test of concept trials ....................................................................................................37 AIDS vaccines for adolescents ........................................................................................39 An interview with… Zackie Achmat ..................................................................................43 Understanding… other HIV prevention strategies Cutting HIV transmission ................................................................................................47 Treatment as prevention ..................................................................................................52 Capping infection ............................................................................................................56 HIV prevention in a pill? ..................................................................................................61 An interview with… Stephen Lewis ....................................................................................65 Understanding… other vaccines Cervical cancer vaccines ..................................................................................................70 Malaria vaccines: Renewed promise ................................................................................73 Rotavirus: Vaccines enter battle against an intestinal virus ..........................................77 www.iavireport.org Understanding… the science of AIDS vaccines …the early stages of HIV infection How can studying what happens immediately following HIV infection help researchers design an AIDS vaccine? By Kristen Jill Kresge here are many reasons why HIV is such a the CD4+ T-cell count is dangerously low, the Tdifficult virus to combat (Figure 1). One is immune system is incapable of defending the that HIV directly attacks the human immune body from attack by other pathogens and a per- system, the body’s defense against pathogens son also becomes susceptible to many oppor- like viruses and bacteria. The primary target of tunistic infections, which can be deadly. HIV is the CD4+ T cells, an important immune Measuring the number of CD4+ T cells in the cell that directs the body’s response to an infec- blood is a convenient way for researchers to esti- tion. During HIV infection huge numbers of mate the damage HIV is doing to the immune these cells are infected and killed each day, but system, since blood samples are easily obtained. new ones take their place. But the majority of the body’s CD4+ T cells Doctors or nurses can monitor the progres- aren’t in the blood. Rather they are found in the sion of HIV disease by CD4+ T-cell counts, mucosal tissues, such as those lining the respira- which are a measure of the number of CD4+ T tory, gastrointestinal, and genital tracts. Looking cells circulating in the blood. For many years only at the blood may paint an inaccurate picture after initial infection the quantity of these of what is really happening during HIV infec- important immune cells can stay the same or tion, so researchers have recently focused