IMPORTANCE OF ANTIBODY ISOTYPE IN VAGINAL HIV TRANSMISSION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 现在很清楚，肠道和其他粘膜组织在HIV感染的传播和早期发病机制中都起着重要的作用。这些研究最初是为了确定不同同种类型的抗体是否更好地保护阴道穹隆，并进行了实验以确定是否存在优先分泌，我们现在已经证明，静脉给药后，HIV特异性IgA和Ig G分别优先从肠(直肠)和阴道分泌，并且在给猕猴注射后6-12小时，在粘膜组织中可以检测到高达10ug/ml的单抗。然而，在非肠道给药后，我们不能在阴道内检测到足够的IgA分泌，这与阴道分泌物中大量产生IgA的假设一致。虽然信息丰富，但这阻碍了最初研究的完成，我们现在已经转向探索粘膜抗体保护的机制，特别是MPER抗体。

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. It is now clear that intestine and other mucosal tissues are of major importance in both the transmission as well as the early pathogenesis of HIV infection. These studies were initiated to determine if antibodies of different isotypes were better for protecting the vaginal vault, and performed experiments to determine if there was preferential secretion and we have now demonstrated that HIV-specific IgA and IgG are preferentially secreted from the intestine (rectum) and vagina, respectively following intravenous administration, and that following parenteral administration, up to 10ug/ml monoclonal antibodies can be detected in mucosal tissues 6-12 hr after administration to macaques. However, we could not detect sufficient IgA secretion in the vagina after parenteral administration, consistent with the hypothesis that IgA is produced in significant quantities in vaginal secretions. Although informative, this prevented the original study from completion and we have now switched directions to pursuing mechanisms of mucosal antibody protection, especially with MPER antibodies.