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

这个子项目是许多利用 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。 A.具体目标 1.比较不同免疫水平猕猴对SIV/SHIV感染的抗原特异性伊加、IgG和IgM免疫应答的作用。我们将比较静脉内、阴道内和直肠内接种SIVmac 251（一种持续导致持续病毒血症和AIDS的高致病性病毒）的猕猴与粘膜接种低剂量SHIVsf 162 p3（其通常导致低至不可检测的血浆病毒血症和缺乏疾病进展）的猕猴中的抗原特异性伊加和IgG应答。还将在SIVmac 251接种的猕猴中评估抗原特异性免疫球蛋白应答，所述猕猴能够控制其感染并成为长期非进展者（LNTP）。 2：通过不同途径感染SIV的猕猴体内效应记忆B细胞的数量。由于粘膜免疫系统被“区室化”为粘膜和全身性武器，我们假设粘膜免疫反应可能会有所不同，这取决于接种途径。因此，将在不同组织中评价和定量效应记忆B细胞，包括静脉和粘膜接种猕猴的外周血、肠、淋巴结和BAL样品。 我们还将定量来自全身和粘膜免疫部位的分泌型伊加和IgG。使用这种方法，我们预测，我们将能够将SIV特异性粘膜免疫反应与减少病毒血症和保护感染致病病毒的猕猴免于疾病进展相关联。

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. A. SPECIFIC AIMS 1: To compare the role of antigen specific IgA, IgG and IgM immune responses in macaques with different levels of immunity to SIV/SHIV infection. We will compare antigen specific IgA & IgG responses in macaques intravenously, intravaginally, and intrarectally inoculated with SIVmac251 (a highly pathogenic virus that consistently results in persistent viremia and AIDS) to macaques mucosally inoculated with low doses of SHIVsf162p3 (which usually results in low to undetectable plasma viremia and lack of disease progression). Antigen specific immunoglobulin responses will also be assessed in SIVmac251 inoculated macaques, which are able to control their infection and become long-term nonprogressors (LNTP). 2: To quantify effector memory B cells in macaques infected with SIV by different inoculation routes. Since the mucosal immune system is "compartmentalized" into mucosal and systemic arms, we hypothesize that mucosal immune responses may differ depending on the route of inoculation. Thus, effector memory B cells will be evaluated and quantified in different tissues including peripheral blood, intestines, lymph nodes, and BAL samples of intravenously and mucosally inoculated macaques. We will also quantify secretory IgA and IgG from both systemic and mucosal immune sites. Using this approach, we predict that we will be able to correlate SIV specific mucosal immune responses with reduction of viremia and protection from disease progression in macaques infected with pathogenic viruses.