ROLE OF ANTIBODY IN PERINATAL TRANSMISSION OF SHIV

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 艾滋病毒母婴传播是全世界婴儿死亡和发病的一个重要原因，使几十年来在婴儿存活方面取得的进展发生逆转。我们一直在研究母体中和抗体（NAb）在限制感染或发病机制中的作用。我们正在用致病性SHIV经口感染新生婴儿猕猴，并给予被动获得的SHIV特异性IgG来模拟母体IgG。 我们监测疾病的进程和新生儿对SHIV产生的免疫反应。我们正在比较与攻毒病毒中和的匹配IgG和与攻毒病毒中和活性有限的不匹配IgG。这项研究还将使我们能够确定是否存在中和与非中和IgG影响的程度或时间的NAb感染的婴儿。 在过去的一年中，我们已经表明，匹配的IgG治疗导致病毒控制和NAb和ADCVI的加速发展，这是一项新的发现，对HIV阳性母亲所生新生儿的HIV-1传播和控制具有重要意义。 我们正在使用相同的SHIV分离株和被动IgG，包括人中和单克隆抗体，在年轻的恒河猴中扩展和确认这些发现。

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.