The goal of this proposal will be to probe the HIV-1 specific B cell repertoire of rhesus monkeys infected with chimeric simian-human immunodeficiency viruses (SHIVs) by developing a large panel of rhesus monoclonal antibodies (RhMAbs) that recognize envelope glycoproteins of HIV-1. The RhMAbs will be characterized with respect to epitope mapping, strain reactivity, and functional activity in vitro. The rhesus Mabs will be compared with our existing panel of human MAbs to HIV-1 surface glycoproteins in order to determine to what extent B cell responses elicited in SHIV infected monkeys are the same or different from that occurring in patients infected with HIV-1. This is an important question which bears on the relevancy of the SHIV model to studies of HIV-1 pathogenesis and vaccine efficacy to human disease. In addition, rhesus MAbs that have particularly potent neutralizing activity against HIV-1 in vitro can be used in a carefully modeled system to determine whether such antibodies are capable to protecting naïve monkeys from challenge with pathogenic SHIVs. Finally, novel MAbs may be developed which are quite different from HMAbs generated from HIV-1 infected patients and these MAbs have usefulness in further investigations of the structure and function of HIV-1 envelope glycoproteins.
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