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