The long-range goal of this HIVRAD Program Project is to develop vaccine strategies against mucosal HIV clade C transmission, with a special focus on identifying conserved regions on HIV clade C envelope glycoproteins that are targets for neutralizing antibodies (nAbs). The overall objectives for Core C (Primate Studies) are to provide the experimental animals and support services needed to facilitate the efficient completion of the aims outlined in Project 1 and Core A (molecular evolution of HIV clade C envelope genes in humans and primates), Project 2 (isolating neutralizing monoclonal antibodies and mimotopes), and Project 3 (recombinant replication-competent adenovirus prime/protein boost vaccination). This will include the provision of retrovirus-free juvenile and infant rhesus macaques from the Yerkes rhesus macaque breeding colonies;adaptation of novel chimeric simian-human immunodeficiency virus (SHIV) constructs that encode various HIV clade C env genes (SHIVenvC strains) to rhesus macaques (Core A);titration of SHIVenvC strains by the intrarectal and oral routes to provide vaccine challenge stocks (Project 3) and assessment of viral pathogenicity in infant and juvenile animals;collection of blood and bone marrow samples from monkeys with broadly reactive nAb responses (Project 2);and immunization and mucosal challenges of rhesus monkeys (Project 3). Core C tasks also include daily monitoring of the experimental animals;periodic physical examinations with blood collections for immunologic and virologic evaluations and shipment of samples to the Program Project investigators;the performance of CBCs and flow cytometry evaluation to determine lymphocyte subsets;and the performance of a basic gross and histologic necropsy evaluations of all experimental animals that die or are sacrificed during the course of this study. Provision of these resources and support services will facilitate the development and testing of the novel AIDS vaccine concepts proposed in this Program Project. Core C studies will play a key role in the establishment of a biologically relevant R5 SHIVenvC model of mucosal transmission and pathogenicity, and will allow evaluation of vaccine efficacy with either prevention of infection (sterilizing immunity) or significant modulation of post-challenge viral loads and immunological parameters as criteria of vaccine efficacy.
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