This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mother-to-child transmission of HIV is a significant cause of infant mortality and morbidity worldwide, reversing the decades of progress in infant survival. We have been studying the role of maternal neutralizing antibodies (NAbs) in limiting infection or pathogenesis. We are infecting newborn infant macaques 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. We are comparing neutralizing Matched IgG to the challenge virus and Mismatched IgG with limited 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 NAbs in infected infants. In the last year we have shown that treatment with Matched IgG results in viral control and accelerated development of NAbs and ADCVI, a novel finding that has significant implications for HIV-1 transmission and control in newborns born to HIV-positive mothers. We are in the process of extending and confirming these findings in young rhesus macaques, using the same SHIV isolate and passive IgG, including human neutralizing monoclonal antibodies.
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