This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Mother-to-child transmission of HIV is a significant cause of infant mortality and morbidity worldwide, reversing the decades of progress in infant survival. The long-term goal of our research is to limit transmission or disease progression in infants by augmenting maternal and infant immunity through vaccination or monoclonal therapy. We have been investigating perinatal transmission of a mucosally transmitted SHIV in macaques and studying the role of maternal neutralizing antibodies in limiting infection or pathogenesis in newborn infant macaques. We have previously shown that passively acquired IgG with neutralizing activity has a highly beneficial effect on health and the ability of animals to mount a strong antiviral response. We are infecting newborn infants orally with pathogenic SHIV and administering passively acquired SHIV-specific IgG to simulate maternal IgG. We monitor the disease course and the immune responses generated to SHIV in the newborns. To determine the role of maternal polyclonal antiviral IgG (SHIVIG) in limiting infection, we are comparing neutralizing IgG matched to the challenge virus and mismatched IgG with limited or no neutralizing activity against the challenge virus. This study will also allow us to determine whether the presence of neutralizing versus non-neutralizing IgG affects the magnitude or timing of neutralizing antibodies in infected infants. The long-term goal is to investigate mechanisms of action of viral control and the development of an accelerated neutralizing antibody response. This SHIV-macaque model offers potential for understanding the role of immune control and tissue distribution of individual variants, as well as antiviral immunity.
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