IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在HIV暴露和感染个体中的病毒特异性免疫应答研究以及猴SIV疫苗研究表明，刺激免疫系统单臂的疫苗方法不太可能提供有效的病毒感染保护。几项研究表明，强的CD 8+细胞毒性T淋巴细胞（CTL）反应可能由感染或候选疫苗引起，这可能与病毒载量的边际降低相关，但这些与感染或疾病进展的保护无关。 然而，除了CTL外，B淋巴细胞也通过分泌中和和非中和抗体来对抗入侵的病原体，在对感染的免疫应答中发挥重要作用。此外，一些新的发现表明，SIV特异性伊加反应在粘膜和外周免疫区室是重要的，在控制病毒感染。最近的报道还表明，抗体与抗原结合的特异性和定量性质在确定抗体的中和活性中起重要作用。因此，我们假设，与具有持续病毒血症并进展为AIDS的动物相比，在病毒载量降低或检测不到的动物中将观察到抗原特异性免疫球蛋白（IG）应答的质量差异。我们还假设抗原抗体结合特性和组织中抗原特异性效应记忆B细胞或分泌型IG的水平将与SIV感染猕猴中病毒载量的减少或疾病进展相关。在拟议的研究中，我们将检查和比较SIV特异性伊加，IgG和IgM免疫反应和抗体结合特性的外周血，粘膜分泌物的猕猴接种SIVmac 251和/或SHIVsf 162 p3。我们还将检测SIV感染猕猴外周血、支气管肺泡灌洗液、骨髓、小肠和淋巴结组织中记忆B细胞的效应功能。

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. Studies of virus specific immune responses in HIV exposed and infected individuals as well as SIV vaccine studies in monkeys suggest that it is unlikely that vaccine approaches that stimulate a single arm of the immune system will provide effective protection from viral infection. Several studies have shown that strong CD8+ cytotoxic T lymphocytes (CTL) responses may be elicited by infection or vaccine candidates, which may correlate with marginal decreases in viral loads, yet these do not correlate with protection from infection or disease progression. However, In addition to CTL, B-lymphocytes also play an important role in the immune response to infection by secreting neutralizing and non-neutralizing antibodies to combat invading pathogens. In addition, several new findings suggest SIV-specific IgA responses in mucosal and peripheral immune compartments are important in controlling viral infection. Recent reports have also shown that the specificity and quantitative properties of antibody binding to antigen plays an important role in determining the neutralizing activity of the antibody. Thus we hypothesize that differences in the quality of antigen specific immunoglobulin (Ig) responses will be observed in animals in which viral loads are reduced or undetectable compared to animals that have persistent viremia and progress to AIDS. We also hypothesize that the level of antigen-antibody binding properties and antigen-specific effector memory B cells in tissues or secretory Ig will correlate with the reduction of viral load or disease progression in SIV infected macaques. In the proposed studies, we will examine and compare SIV-specific IgA, IgG and IgM immune responses and antibody binding properties in peripheral blood, and mucosal secretions of macaques inoculated with SIVmac251 and/or SHIVsf162p3. We will also examine the effector function of memory B cells in peripheral blood, broncho-alveolar lavage, bone marrow, small intestine and lymph node tissues from SIV infected macaques.