Structuring an Effective AIDS Vaccine

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Gary Nabel, MD, PhD

Director, Vaccine Research Center National Institute of Allergy and Infectious Diseases

Though antiviral drugs have shown promise in preventing HIV infection recently, a vaccine represents the single most important intervention that could hasten the end of the AIDS pandemic. The development of a vaccine poses an exceptional research challenge, and progress has been slow, but among developments that have renewed optimism has been the isolation of exceptionally broadly neutralizing antibodies derived from HIV-infected subjects. At the VRC, we have used structure-based rational vaccine design to identify a human antibody, termed VRC01, which neutralizes more than 90% of naturally circulating viruses. Thousands of additional related antibodies have now been defined by deep sequencing. They recognized the highly conserved CD4bs of the viral envelop required for entry. Understanding how this antibody recognizes the virus and how it is generated provides critical insight into the design of an AIDS vaccine. Such monoclonal antibodies also confer passive protection against lentiviral infection in nonhuman primates and can be used to develop novel immune-based prevention strategies. A combination of lack of a predictive animal model and as yet undefined biomarkers of HIV protection necessitate that clinical trials, including active vaccination and passive protection, be performed to define an effective vaccine.

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