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. The overall objective of this project is to examine immune responses elicited by different 'prime-boost' immunization strategies and to identify combinations that effectively induce both antibody and CD8+ T cell-mediated immune responses against primate lentiviruses. Since different immunization modalities activate different responses, we hypothesize that a combination of immunization modalities ('prime and boost') offers the best likelihood of inducing the balanced immune responses required for vaccine protection. Three modalities of immunization will be evaluated: live virus vectored vaccines, DNA vaccines, and subunit protein vaccines. The first stage of this experiment utilizes 24 M. nemestrina to examine immune responses elicited by priming with recombinant vaccinia virus and boosting with protein, DNA or recombinant virus . Eighteen macaques were immunized with two recombinant vaccinia viruses, one expressing SIVmac239 gag-pol and the other HIV-1 SF162 env. Six macaques were immunized with parental vaccinia virus as control. All 18 animals in the experimental group have detectable HIV Env-specific antibody responses after 2 immunizations, whereas none of the control animals showed any reactivity. Vector specific responses were quantified by TNF-alpha and INF-gamma producing cells by flow cytometric analysis. Data demonstrate low levels of vector specific and vaccine specific responses were detected and that these responses were stably maintained at least up to 16 weeks post priming. Animals will be boosted with three different immunogens (protein, DNA and virus vector) before being challenged with SHIV162 P4 to determine their protective efficacy.
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