Wisconsin National Primate Research Center Support

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DESCRIPTION (provided by applicant): Understanding the immunological and genetic basis of control of AIDS virus replication should help inform vaccine design. As in HIV-infected humans, a limited number of macaques spontaneously control SIV replication to less than 1,000 copies/ml after infection ("Elite Controllers"; ECs) (18, 32). This is a greater than two log reduction from the typical plasma virus load after challenge with SIVmac239. Recently we identified sixteen ECs in a cohort of 196 Indian rhesus macaques (18). Genotyping for MHC class I alleles revealed that fourteen of these sixteen ECs expressed either Mamu-B*17 or Mamu-B*08, which appear to be the macaque functional equivalents of HLA-B57 and HLA-B27, respectively (2, 9, 12, 21, 26, 29). However, the monitoring and sampling of these animals, which were typically identified in the course of experiments run by different investigators, has not been consistent. Moreover, due to financial constraints, animals often must be euthanized at the end of specific studies. We plan to establish a sample bank, database, and to house existing and future EC macaques at the WNPRC. Making these unique resources available to the community of investigators working on SIV would be an extremely valuable service to the field. Component Critique Significance: One of the biggest obstacles for HIV vaccine development is the lack of a clear understanding of the immune correlates for protection. Therefore, attempts to understand the potential mechanisms underlying apparent clinical protection in certain rare individuals (both human and macaque) who naturally exhibit protection without vaccination are highly significant. Studying elite controllers (ECs) of HIV replication is complicated by the fact that additional variables come into play, such as viral heterogeneity and the inability to know the source and timing of the infection. In contrast, NHP model studies allow uniformity of the viral inoculum by employing a single molecularly cloned virus