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

抗原特异性 IGA 反应在控制 SIV/SHIV 感染中的重要性

• 批准号: 8359778
• 负责人: Bapi Pahar
• 金额: $ 45.19万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359778
• 关键词: Acquired Immunodeficiency Syndrome; Antigens; Disease Progression; Dose; Funding; Grant; Immune; Immune response; Immune system; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infection; Infectious Diseases Research; Intestines; Macaca; Memory B-Lymphocyte; Mucosal Immune Responses; National Center for Research Resources; Plasma; Principal Investigator; Research; Research Infrastructure; Resources; Role; Route; SIV; Sampling; Secretory Immunoglobulin A; Site; Source; Tissues; United States National Institutes of Health; Viremia; Virus; arm; cost; lymph nodes; peripheral blood; response; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 A. 具体目标 图1：比较不同免疫水平的猕猴对SIV/SHIV感染的抗原特异性IgA、IgG和IgM免疫反应的作用。我们将比较静脉内、阴道内和直肠内接种 SIVmac251（一种高致病性病毒，始终导致持续性病毒血症和艾滋病）的猕猴与粘膜接种低剂量 SHIVsf162p3（通常导致低至低剂量）的猕猴的抗原特异性 IgA 和 IgG 反应。无法检测到的血浆病毒血症和缺乏疾病进展）。还将在接种 SIVmac251 的猕猴中评估抗原特异性免疫球蛋白反应，这些猕猴能够控制感染并成为长期不进展者 (LNTP)。 图 2：量化通过不同接种途径感染 SIV 的猕猴中的效应记忆 B 细胞。由于粘膜免疫系统被“划分”为粘膜免疫系统和全身免疫系统，我们假设粘膜免疫反应可能因接种途径而异。因此，将在不同组织中评估和量化效应记忆 B 细胞，包括静脉和粘膜接种的猕猴的外周血、肠道、淋巴结和 BAL 样本。 我们还将量化系统和粘膜免疫位点的分泌型 IgA 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病毒血症的减少和感染病原病毒的猕猴免受疾病进展联系起来。