USE OF THE SHIV AND SIV MODELS OF AIDS FOR HIV VACCINE DEVELOPMENT

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Failures to date in our effort to create an effective AIDS vaccine can be explained, at least in part, by two shortcomings: (1) a lack of appreciation of the potential importance of virus-specific cell-mediated immunity in preventing HIV-1 infection, and (2) an inability to overcome the problem of viral diversity. Recent advances in our understanding of vaccine technologies that can elicit effector T cell responses and the development of important new non-human primate model systems for studying AIDS vaccine development make it possible now to begin addressing some of these issues in a meaningful way. We have shown now that peptides, live recombinant organisms and plasmid DNA can licit AIDS virus-specific CTL in higher primate species. We have also developed a chimeric virus expressing a primary patient HIV-1 envelope on an SIVmac backbone that can infect and induce AIDS in macaque species. These tools will be harnessed in the proposed studies to explore in rhesus monkeys: 1. HIV-1 envelope V3 loop peptide-elicited immunity 2. Vaccination to broaden CTL recognition of variant viruses 3. Cytokine profiles of CD4+ T cells following infections and vaccinations 4. Novel HIV vaccine strategies.