HIV VACCINE RATIONALE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. We focus on an HIV-1 vaccine cocktail strategy, prompted by cocktail vaccine successes in other fields. The multi-vectored, multi-envelope vaccine strategy elicits HIV-1-specific B- and T-cell functions (measured by antibody binding, neutralization, antibody-dependent cell-mediated cytotoxicity and gamma interferon assays), with a diversity and durability that may be required to prevent HIV-1 infections in humans. Based on the success of previous vaccine studies at TNPRC, in this study we will compare the efficacy of 4 vaccine protocols to unvaccinated control animals. Animals were vaccinated with a combination of some or all of DNA, live and killed recombinant vaccinia virus expressing HIV-env, and HIV protein. Assays measuring cellular and humoral immune response indicate a strong, broadly based immune response to SHIV. Animals will be challenged with SHIV to assess vaccine efficacy in vivo.