Non Human Primate Core and the S. dysenteriae Vaccine Development Study - MARGE

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Optimal utilization of nonhuman primates for biodefense research requires a facility whereby animals are housed in appropriate biocontainment, research personnel experienced in the methodologies required for infectious disease research and vaccine development, and development of the necessary reagents to perform state-of-the-art immunological research. The breadth and magnitude of these responsibilities are best met by a consortium of more than one institution. Toward this end, the primate facilities at the University of Pittsburgh and the University of Maryland are sharing in these efforts. Specifically, we shall provide state-of-the-art BSL3 facilities for nonhuman primates. We shall also make available our extensive experience in the utilization of nonhuman primates for pathogenesis research and vaccine development for AIDS, tuberculosis, and other infectious agents for use in similar studies with category A/B agents. Further, we will provide the necessary reagents for analysis of immune function for use in cynomolgus macaque species. Cynomolgus macaques provide ideal models for infection with category A/B agents because they are both susceptible to infection with these agents and are readily available. However, some of the reagents required for evaluating the immune responses in this species are lacking. We propose to address these limitations by the following: 1. The MHC class I loci of cynomolgus macaques will be genetically characterized, and the loci found most common in the population identified. Peptide binding motifs specific for Category A agents will be further determined for use as reagents in T cell assays to better define and quantify the specificity of the immune response and to track effector populations to mucosal tissues. These studies will be performed through collaboration with scientists at the University of Pittsburgh and those at Epimmune, Inc. who have pioneered this effort in the rhesus macaque. 2. Cytokine/chemokine microarrays specific for cynomolgus macaques will be developed for evaluating pathogenic mechanisms and for analysis of immune responses to vaccines. 3. A primate model for mucosal vaccination using a Shigella dysenteriae challenge will be developed at the University of Maryland and characterized as a part of the above collaboration. Together, these efforts will provide an ideal setting with which to develop and test the methodologies proposed in this application.