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。 对接触艾滋病毒和感染艾滋病毒的人的病毒特异性免疫反应的研究以及对猴子的SIV疫苗研究表明，刺激免疫系统的单个手臂的疫苗方法不太可能提供有效的保护，使其免受病毒感染。一些研究表明，感染或候选疫苗可能会激发强烈的CD8+细胞毒性T淋巴细胞(CTL)反应，这可能与病毒载量的轻微下降有关，但与预防感染或疾病进展无关。然而，除了CTL，B淋巴细胞还通过分泌中和抗体和非中和抗体来对抗入侵的病原体，在感染的免疫反应中也发挥着重要作用。此外，一些新的发现表明，粘膜和外周免疫隔间中的SIV特异性IgA反应在控制病毒感染方面具有重要意义。最近的报道也表明，抗体与抗原结合的特异性和定量性质在决定抗体的中和活性方面起着重要作用。因此，我们假设，与持续性病毒血症和进展为艾滋病的动物相比，病毒载量减少或检测不到的动物的抗原特异性免疫球蛋白(Ig)反应的质量将有所不同。我们还假设，组织或分泌Ig中的抗原-抗体结合特性和抗原特异性效应记忆B细胞的水平将与SIV感染猕猴的病毒载量减少或疾病进展相关。在拟议的研究中，我们将检测和比较接种SIVmac251和/或SHIVsf162p3的猕猴外周血和粘膜分泌物中SIV特异性IgA、Ig G和Ig M的免疫反应和抗体结合特性。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.