With accruing data indicating the critical importance of cytotoxic T lymphocytes (CTL) in containing the replication of HIV-1 in infected individuals, AIDS vaccine strategies are being evaluated in pre-clinical studies that elicit high frequency cell-mediated immune responses. Among the most impressive of these HIV-1 vaccine modalities that have been assessed to date in nonhuman primate models are the gene-deleted human adenovirus vectors. However, there is concern that pre-existing immunity to adenoviruses in vaccinees may substantially decrease the immunogenicity of such vaccine constructs. Pre-existing immunity to common serotype adenoviruses is, in fact, quite common in human populations. Therefore, these vaccine constructs may prove to be less than optimal immunogens in humans. Adenoviruses from nonhuman primate species may provide vectors that elicit immunity comparable to that elicited by recombinant human adenovirus constructs. These constructs may prove particularly useful as human immunogens since immunity to these vectors should not exist in human populations. The studies described in the present proposal assess the immunogenicity of recombinant chimpanzee adenovirus vaccine constructs in macaques. The immunogenicity of these vectors will be determined, strategies for their optimal use will be explored, and their protective efficacy will be examined. Specifically, we will assess the: I. Immunogenicity of recombinant chimpanzee adenoviruses in macaques; I1.Prime/boost strategies for vaccination using recombinant chimpanzee adenovirus constructs; II1.Impact of pre-existing immunity to human adenoviruses on immunogenicity of recombinant chimpanzee adenovirus vaccines; IV. Relative immunogenicity of various prime/boost strategies; V. Protection of recombinant chimpanzee adenovirus immunized monkeys against challenge with a) athogenic clade C SHIV.
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