PROJECT SUMMARY/ABSTRACT: The primary goal of this application is to sustain the Specific Pathogen Free (SPF) program at the Caribbean Primate Research Center (CPRC) through the support of operations, administration, veterinary care, virological and MHC typing, and by the improvement of our comprehensive genetic management plan. Animals' characterization, both for the virology profile and MHC typing, is performed by state-of-the-art methodologies. A unique feature of CPRC animals in favoring a successful establishment and sustainability of SPF colony is that these animals are naturally free of SIV and SRV-D, two of the four viruses to be tested. Nevertheless, we continue systematically testing for all four viruses (B virus, STLV, SIV, and SRV-D) for safety and as required for the SPF Program. The Program provides unadmixed Indian-origin rhesus monkeys with a defined genetic and virological background. The population genetic analyses revealed that the SPF colony has remained genetically homogenous over time with sufficient heterozygosity and minimal stratification from its non-SPF founders. Genetic variation will be maintained in the SPF colony using the genetic management strategies described in this application. The genetic management approach will allow for the enrichment of desired MHC markers in demand for biomedical research while maintaining genetic diversity. Our genetic management approach will be concordant with the NIH's National NHP Genetics and Genomics Consortium guidelines for ensuring the long-term viability of the CPRC's SPF colony. The estimates of Indian ancestry among the SSFS SPF colony animals are also among the highest that has been calculated across several National Primate Research Centers in the US. Funds are requested in this application to sustain the SPF program and to meet the proposed aims. With continued NIH support, Institutional contribution, and funds from the program income, the SPF program at CPRC will remain a significant national research resource. They will be able to provide healthy SPF Indian-origin rhesus monkeys of defined genetic and virological background to NIH-sponsored research programs. The Covid-19 pandemic poses high pressure on the demand for rhesus macaques. The U42 at CPRC supported the development of some of the Covid-19 vaccine formulations in the market. Currently, the demand continues to exceed the SPF animal's availability. However, our Program has supported several investigators conducting cutting-edge research on HIV and AIDS-related research projects in various areas, including pathobiology, characterization of the immune response, con-infections, and comorbidities, development of new HIV/AIDS vaccines and therapeutic approaches, including microbicides, among others.