Project Summary, Overall “Expanded SPF Rhesus Macaque Breeding Colony for AIDS Research” The Indian rhesus macaque (Macaca mulatta) develops a disease that closely mimics human acquired immunodeficiency syndrome (AIDS) when infected by simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency viruses (SHIV), and represents the best animal model for HIV infection. Preclinical vaccine development is heavily dependent on the SIV and SHIV rhesus macaque models. The value and utility of the model are markedly enhanced by improving the level of microbial and genetic characterization. Macaques free of ubiquitous viruses that are homologues of human viruses responsible for opportunistic infections are essential for a growing number of AIDS-related opportunistic infection models and for viral vaccine vector development based on these agents. The utility of macaque models for immunological research has been hindered by the unprecedented complexity of their major histocompatibility complexes. Comprehensive MHC genotyping has the potential to revolutionize the use of macaques in infectious disease research and to guide functional immunology studies. MHC-restricted cellular immune responses are crucial in protective immunity and resistance to infectious diseases. The comprehensive objective of this application is to increase the capacity of the ONPRC AIDS Research Expanded SPF Breeding Colony to provide genetically characterized Indian-origin rhesus macaques free of a broad number of enzootic and zoonotic agents to enhance the usefulness of the resource for cutting edge opportunistic agent and vaccine research.