The Nonhuman Primate Core, Core B, will provide personnel and assays for all preclinical testing of candidate vaccines in pig-tailed macaques (Macaca nemestrina). SlV antigens for evaluation as immunogens will be developed by Drs. Hahn and Compans, as described in Projects 1 and 2, respectively, and will include SlVmac239 and SIVsm/mac consensus sequence Env and Gag virus-like particles as well as DNA and recombinant adenovirus vectors. Novel adjuvants, initially screened in mice by Drs. Moldoveanu and Mestecky, Project 4, also will be tested for enhancement of both systemic and mucosal immune responses. Each experimental protocol will consist of immunizing macaques by intradermal and/or intranasal inoculation of immunogens, characterizing SlV-specific humeral and cellular immune responses in blood and mucosal secretions, challenging macaques by either intravenous or intrarectal routes with a pathogenic SlY strain, and assessing the level of protection. During the immunization period, SIV-specific humoral and cellular immune responses will be evaluated for production of lgG, IgA, and neutralizing antibodies and for antigen-specific proliferative responses of lymphocytes. Some blood samples will be sent to Dr. Letvin's laboratory (Project 3) for analysis of interferon-g production by lymphocytes in response to peptide pools representing the entire gag gene. After inoculation of live virus, regular assessment of the macaques for virus burdens and signs of disease, such as rash, lymphadenopathy, or weight loss, will be done. These assays will include qualitative and quantitative analyses of virus burden, antibody production, and various hematologic parameters, including absolute numbers of T-cell subsets and platelets. Plasma levels of SIV virion RNA will be determined by QC-RT-PCR in Dr. Jeff Lifson's laboratory at the NCI-Frederick Cancer Research Center. The overall goal of the Program Project is to develop an effective HIV vaccine that will prevent infection or disease. To identify the best immunogens, adjuvants, and routes of immunization, initial testing of vaccine strategies in the SlV-macaque model is critical before intelligent decisions can be made regarding selection of candidate HIV vaccines for use in Phase I human trials. Thus, the Nonhuman Primate Core is critical for the success of this program project grant.
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