This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Passive studies utilizing neutralizing antibodies (NAbs) in non-human primate models for HIV have shown that high doses of NAbs can fully block infection by either intravenous or mucosal challenge. Although it may be difficult to attain such high levels of NAbs in humans through maternal transfer or vaccination, there is evidence that even non-sterilizing levels of NAbs can reduce the infectivity of viruses in vivo and ameliorate disease. Non-human primate models have been used to test passive NAbs as immediate post-exposure treatments. Our group showed that high dose IgG can both control the pathogenic SIV and also accelerate the development of NAbs. We have also analyzed the development of NAbs in adult and newborn macaques infected with another virus, SHIV-SF162. We found that passive NAbs triggered the development of NAbs that appeared sooner and were higher in titer than those that developed in untreated controls. In this proposal, we plan to isolate and characterize individual monoclonal antibodies (mAbs) cloned from macaque B cells and to compare them with the polyclonal NAbs that develop in these macaques. This work will develop useful neutralizing human mAbs and will contribute to understanding how antibody-based therapy can limit Mother-to-child transmission of HIV.
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