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。根据我们早期的工作，我们假设粘膜免疫反应，特别是由IgA介导的体液免疫反应，对控制HIV感染可能比全身免疫反应(如免疫球蛋白)更重要。为了验证这一假设，我们最近进行了一项研究，该研究设计了一种带有IgA重链的抗HIV单抗，并系统地将其注入猕猴体内，以确定与同一抗体的天然形式(Ig G)相比，该抗体在粘膜表面是否会有更多的分泌。我们已经完成了这些实验，目前正在检查从这些动物身上收集的粘膜拭子，以进行免疫球蛋白定量评估。如果我们发现这种抗体在免疫球蛋白A同型时的分泌水平确实高于免疫球蛋白同型，我们将进行挑战性研究，看看这些粘膜抗体是否提供了比免疫球蛋白同型更好的保护作用。这可能与艾滋病毒疫苗设计高度相关。

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 the the intestine and other mucosal tissues are of major importance in both the transmission as well as the early pathogenesis of HIV infection. Based on our earlier work, we have hypothesized that mucosal immune responses, particularly humoral immune responses mediated by IgA, may be more important for controlling HIV infection than systemic immune responses such as IgG. To test this hypothesis, we have recently performed a study in which an anti-HIV monoclonal antibody was designed with an IgA heavy chain and systemically infused into macaques to determine if there would be greater secretion of this antibody in mucosal surfaces compared to the same antibody in its native (IgG) form. We have completed these experiments and are currently examining mucosal swabs collected from these animals for quantitative immunoglobulin assessment. If we find that this antibody when in an IgA isotype is indeed secreted in higher levels than the IgG isotype, we will perfom challenge studies to see if these mucosal antibodies provide better protection than IgG isotypes. This could be highly relevant for HIV vaccine design.