The development of a safe and effective HIV-1 vaccine is of clear importance and, because of limitation with traditional approaches, new approaches such as DNA vaccines need to be evaluated. Three novel methods will be tried to improve the efficiency of DNA vaccination for HIV-1. First, the delivery of DNA vaccines will be optimized by targeting directly to dendritic cells in vivo. Second, the low immunogenicity of the HIV-1 env protein will be increased by optimization of the translation codons as well as targeting to MHC-1 class processing pathway. Third, a potent costimulating ligand, 4-1 BBL, will be used to amplify antigen-specific cytotoxic cells. The phase I studies will focus on optimizing HIV-1 env DNA vaccine. In phase II studies, the investigator proposes to expand the cocktail vaccine using additional HIV-1 genes such as gag, pol and nef to generate a multi- specific CTL response. Ultimately, they will test the new generation of DNA vaccines for protection against HIV/SIV (SHIV infection in non-human primates).
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