Recent evidence has demonstrated the central role played by cytotoxic T lymphocytes (CTL) in containing HIV-1 replication. It is, therefore, becoming increasingly important to have technologies available for evaluating these immune responses in non-human primate AIDS models. Characterization of these cellular responses during experimental infection in animal models will be essential to clarify the immunopathogenesis of HIV-1 infections. It will also be necessary to measure CTL responses when comparing efficacy and potential utility of candidate AIDS vaccine strategies. To this end, we will explore novel technologies for measuring AIDS virus-specific CTL responses in the rhesus monkey and chimpanzee AIDS models and utilize these immunopathogenesis. In studies described in this application, we will: 1. evaluate fluorescent labeling and flow cytometric enumeration of SIVmac-specific CTL in monkeys using soluble, tetrameric peptide/MHC class I complexes 2. characterize AIDS virus-specific CD8+ T cells in monkeys vaccinated by the mucosal route 3. assess HIV-1-specific CTL responses in infected chimpanzees 4. study novel HIV-1 vaccine strategies in monkeys using polio replicons and virus-like particles.
