IAVI Report THE NEWSLETTER ON INTERNATIONAL AIDS VACCINE RESEARCH VOL 7/NUM 2 MAY–AUGUST 2003 Do Clades Matter for HIV Vaccines? As thousands of people prepare to gather in Nairobi and New York for September’s AIDS meetings, a key question for vaccine developers is how to contend with the huge diversity of HIV strains circulating worldwide BY PATRICIA KAHN is famously the most genetically diverse than anything the public health field has ever attempt- HIVviral pathogen known—nowhere more so ed. Doing it with many different formulations, or with than in Africa—as well as one of the most rapidly repeated updates, would be even more challenging. mutating. That, plus the uneven global distribution of Nailing down the impact of HIV diversity on vac- its nine genetic subtypes, or clades, poses one of the cine responses is difficult, for several reasons. One is biggest scientific unknowns facing AIDS vaccine devel- that the current system for classifying HIV diversity is opers: is a single, “universal” vaccine against all strains based on genetic sequence, not immune properties, possible? Or will it be necessary to make a slew of dif- and hasn’t been translated into distinct “immuno- ferent vaccine formulations, each tailored to the most types”—which is what really matters for vaccines. common strains in a given region? Even worse, could it While that task is slowly being tackled for epitopes tar- Inside: mean that new formulations might be needed regular- geting cellular immunity, it may be impossible for neu- ly, as with flu vaccines? tralizing antibodies (NAbs), where clades don’t seem to In Memoriam: The answer will be key to how quickly, and at correlate with immune recognition. Balla Musa Silla 2 what cost, an AIDS vaccine can be widely distributed Another complication is that the clade issue has around the globe once a successful candidate is identi- become highly politicized. Until recently, vaccine Setting a Scientific fied. Manufacturing even a single formulation and get- development has had a lopsided focus on clade B Agenda for a House on ting it out quickly to adults and adolescents soon after strains, which dominate the epidemic in industrialized Fire: AIDS Prevention it is licensed will be far more complicated and costly countries but cause only about 12% of infections glob- Research Moves Ahead in Russia 3 continued on 2 ▼ Keystone Symposium: Updates on Trials, New NIH DETAILS PLANS FOR ANALYZING Candidates and Immune Basis of VAXGEN PHASE III DATA Protection 7 BY EMILY BASS AIDS Vaccines, from Monkeys to People: t the 24 June meeting of the In the plan’s ongoing first analysis of data with Thai investi- An Interview ANational Institutes of Health phase, an independent team will gators and VaxGen. with John Shiver 10 (NIH) AIDS Vaccine Research re-analyze existing data, looking at Johnston said that NIH devel- Working Group, Peggy Johnston, factors such as race, risk category oped this strategy after VaxGen Studying HIV Diversity head of the NIH AIDS vaccine and the viral strains that infected expressed reluctance to invest in Multi-Clade Regions: research effort, outlined a three- volunteers. A second team is dis- additional funds in the Thai trial. pronged plan for involvement of cussing potential additional analy- At the same meeting, VaxGen rep- Tanzania: At the Cross- NIH and the Centers for Disease ses of blood samples, such as resentative Marc Gurwith said that roads of Africa’s Control (CDC) in VaxGen’s com- broader characterization of anti- the company—which already has Major Clades 17 pleted and ongoing Phase III trials. body responses, and HLA typing. many samples from the nearly- The plan emerged after VaxGen The goal of the third component is completed Thai study—was col- Cameroon: “Final released data from its US- “to ensure completion” of the laborating fully with the independ- Common Pathway” European Phase III study and ongoing Phase III trial in Thailand, ent data analysis. At press time, for a Global Vaccine18 made the controversial claim that Johnston said. To achieve this, precise details of the NIH-initiated the vaccine showed efficacy in NIH, CDC and an as-yet unnamed consortia, and of VaxGen’s role, Vaccine Briefs 20 non-white minority groups. donor will work on statistical had not been specified. ◆ In Memoriam: Balla Musa Silla (1955-2003) Balla Musa Silla, found- Tall, elegant and well-spoken, Mr. Silla had a stately, captivating ing vice-President for presence. A colleague at Partners recalls a plenary speech he once Vaccine Preparedness gave. “Unlike the others on the podium, he had no slides; he simply at the International spoke and told the life story of a girl growing up in poverty. The tale AIDS Vaccine Initiative flowed naturally and illustrated the realities of injustice and the chal- (IAVI), and a visionary lenges to development, but on a deeply personal level. He put the leader in the fields of sentiment back into that auditorium in Geneva—he brought poverty population and interna- into the room. Colleagues from different parts of the world thought tional development, of their own people. This was his gift.” died on 27 June , 2003 Mr. Silla joined IAVI in September 2001, where he founded a at his home in Ossin- department tasked with building international support and aware- ing, New York. He was ness for AIDS vaccine development and helping to build developing 48. The cause of death country capacity for clinical testing. Once again, he proved to be was T-cell lymphoma. equally at home power-brokering with world leaders and listening Mr. Silla was born to the needs and concerns of underserved communities desperate- in The Gambia but ly in need of an AIDS vaccine. Most of all, he understood the cen- was truly a citizen of trality of AIDS in undermining development, as well as the potential the world, having lived and worked in over 27 countries. He was of vaccination to reverse the epidemic’s devastation in the world’s a tireless advocate for the needs and potential of the developing poor countries. world, a theme that runs through his professional and personal Mr. Silla left an indelible impression on those who worked life. His career began in The Gambia, first as a volunteer working with him, and will be remembered for his kindness, generosity of alongside the international community, and eventually as the gov- spirit and dynamic personality. “My memories are of a big, ernment’s Director for Population Affairs, where he was a direct strong, proud man, with a wide, mischievous grin, and a gracious advisor to the President. manner beyond any I have encountered,” says Craig McClure, In 1996, he was approached to lead an ambitious and untested who worked with him at IAVI on community mobilization. To his venture, Partners in Population and Development, an intergovern- former colleagues, he leaves a legacy of commitment to a vision mental alliance of Southern countries addressing issues of family of a better future. planning and reproductive health through South-to-South collabora- Mr. Silla is survived by his wife, Joan Millsap, and their two sons, tion. Partners was a unique organization of Southern governments Christopher and Andrew. working closely with each other and with a variety of NGOs and com- BONNIE BENDER AND FAWZIA RASHEED munity-based groups toward a shared goal. The pace at which the program grew bore witness to Mr. Silla’s deft diplomacy and his Bonnie Bender, IAVI’s Program Manager for Vaccine Preparedness, unstinting commitment to South-South cooperation. His vision was worked with Mr. Silla during his tenure with the organization. Dr. grounded in the belief that the solutions to development lay in devel- Fawzia Rasheed was his colleague at Partners, where she served as oping countries themselves. Senior Advisor on HIV/AIDS & STD and Policy Advisor. ▼ DO CLADES MATTER continued from 1 ally. That disconnect helped mobilize developing coun- cially in Africa.” tries to get involved with HIV vaccine testing, and But despite these challenges, there are promising spurred development of non-clade B candidates— developments, along with some sobering ones. A which now greatly outnumber new clade B-based growing body of data shows that immune responses to ones. But it also helped create a political logjam: Fears T-cell-based HIV vaccines, and to natural infection, that testing vaccines based on “unmatched” strains often recognize HIV proteins from different clades— exploits trial volunteers in developing countries some- fueling optimism that, at least for vaccines targeting cel- times engendered resistance even to early-stage trials of lular immunity, some cross-clade protection can be non-local clades, and raised pressures to tailor vaccine achieved. And studies in infected people are revealing candidates to ever-finer, single-country levels. that a few antibodies which neutralize primary HIV Yet only by comparing vaccine efficacy in strains also work against other clades, findings that are matched settings to partially or completely unmatched renewing hopes of designing immunogens able to elicit ones can the impact of HIV diversity ultimately be NAbs, a task that has long seemed intractable. resolved. Moreover, “a country-by-country approach to Things are also moving on the political front. “I vaccine development would be crippling,” says see a major shift,” says Jose Esparza, coordinator of the Francine McCutchan (Henry M. Jackson Foundation, WHO-UNAIDS HIV Vaccine Initiative, pointing as an Rockville), who leads the US military’s HIV global sur- example to a consensus document on clades released veillance program. “It would make it very, very slow to by the African AIDS Vaccine Programme at its June get vaccines suitable for some hard-hit regions, espe- meeting (see p.