The ultimate objective of this proposal is to develop a multi-component HIV vaccine candidate capable of inducing multiple effector responses to conserved viral epitopes. In this core the immunogenicity of these antigens will be evaluated using different delivery modalities to generate the desired neutralizing antibodies, T-helper and CTL responses especially with regard to mucosal sites. This core (C) will provide the resources as well as the scientific and non-human primate research expertise to evaluate the different vaccine components and delivery systems with regard to cell-mediated and mucosal readouts using outbred MHC characterized Indian rhesus macaques. This core (C) will also evaluate efficacy by challenge and follow-up of the immunized animals in order to correlate vaccine protection with the immune responses induced. Challenge will be performed with well characterized homologous and heterologous pathogenic SHIVs titrated by the vaginal route while IV administration will be used to control for effective parenteral immunization. This core will contribute to the attainment of the objectives by a process of standardized immunogenicity and efficacy testing. The most promising antigens and delivery systems will be selected and optimized for evaluation of efficacy from heterologous mucosal challenge (year 5). This objective will be met by taking the most promising delivery system capable of sustaining durable, long-lasting immune responses. The correlates of immunity observed during the course of this project will guide the selection of the combined vaccine and delivery systems to be used in year 4 and 5. The postchallenge follow-up following each challenge will be supported by the highly sensitive virus detection and quantitation assays provided by this core. Similarly, data derived from standardized state of the art T-helper and CTL assays provided by this core will provide constant feedback to other projects and cores for the head to head comparison of antigens as well as delivery systems provided by the different projects. This system of standardized side by side analysis will provide an unbiased basis for the rational selection of the best vaccine components from each of the different expert groups represented by each of the different projects. This rational approach based on clear stepwise preclinical evaluation and selection based on established performance criteria will provide optimal vaccine candidate(s) for clinical trials.
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