Response to and protection by gp96SIVIg/TNFSF13 and gp96SIVIg/TNFSF15 vaccines

gp96SIVIg/TNFSF13 和 gp96SIVIg/TNFSF15 疫苗的反应和保护

• 批准号: 8198211
• 负责人: ECKHARD R PODACK
• 金额: $ 37.17万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8198211
• 关键词: Animal Model; Animals; Attenuated; B-Lymphocytes; CD8B1 gene; Control Animal; Gene Expression Profiling; Genomics; Goals; HIV vaccine; Histopathology; Human; Human Papillomavirus; Immune; Immune response; Immunity; Immunologics; Infection; Investigation; Kinetics; Link; Macaca mulatta; Modeling; Mucosal Immune Responses; Natural Killer Cells; Nature; Outcome; Phase; Post-Translational Protein Processing; Proteomics; Route; SIV; SIV Vaccines; Surface; T-Lymphocyte; TNFSF15 gene; Vaccinated; Vaccination; Vaccines; Vagina; Viral; Viremia; Virus; Virus Integration; experience; insight; intraperitoneal; lymph nodes; novel vaccines; response; simian immunodeficiency virus gp120; transmission process

Our goal is to determine if we can "outpace" SIV transmission through the induction of a vaccine induced immune response in Rhesus macaques (RM). Two novel vaccines, the gp96-lg-SIV and the HPV-SIV will be administered through intraperitoneal (IP) and intravaginal routes respectively singly or in combination with and without SIV gp120. Our prior experience with these vaccines is that both elicit potent mucosal immune responses through different mechanisms. We hypothesize that the kinetics and nature of mucosal and systemic immune responses will determine the outcome of infection in vaccinated animals following vaginal SIV challenge. Innate and adaptive immune responses will be characterized for each observed outcome to get an understanding of correlates of immune protection. Immunologic studies will be enhanced by concomitant investigation of gene expression profiling, post translational modification, virus diversification and estimates of viral reservoir. Our goal is to understand how natural responses to SIV challenge are altered by vaccines that result in aborted SIV infection or attenuated virus dissemination and lowered peak viremia in vaccinated versus control animals. We are focusing on the vaginal local immunity as well as regional lymph nodes, gut and systemic immune responses. We propose the following aims to evaluate unvaccinated and vaccinated RM pre- and post- challenge with SIVmac251. Aim 1: to investigate innate immune responses, virus integration and virus reservoirs and Aim 2: to investigate adaptive immune responses of CD4 and CD8 T cells and B cells. Studies to be performed will include investigations post vaccination /pre-virus challenge, during the eclipse phase and at 60 days post virus challenge in vaccinated and unvaccinated animals. Exhaustive studies including host restriction factor Apobec3G, viral reservoir, virus diversification, NK cells, gamma-delta T cells, and adaptive SIV specific T and B cell phenotypic and functional profiles will be determined in a carefully coordinated and exhaustive analysis linking genomics, proteomics, histopathology and immunologic analyses to provide insight into earliest mechanisms of host- SIV interaction and correlates of vaccine incused immune protection.

我们的目标是确定我们是否可以通过诱导疫苗诱导SIV的传播， 恒河猴（RM）免疫应答。两种新的疫苗，gp 96-lg-SIV和HPV-SIV将在 分别通过腹膜内（IP）和阴道内途径单独或与 没有SIV gp 120。我们先前使用这些疫苗的经验是， 通过不同的机制来应对。我们假设，粘膜和 全身免疫应答将决定阴道免疫后接种动物的感染结果。 SIV挑战。将针对每个观察到的结果表征先天性和适应性免疫应答， 了解免疫保护的相关性。免疫学研究将得到加强， 基因表达谱、翻译后修饰、病毒多样性的同步研究 和病毒库的估计。我们的目标是了解对SIV挑战的自然反应是如何的 通过疫苗改变，导致SIV感染失败或减毒病毒传播， 接种动物与对照动物的病毒血症。我们关注的是阴道局部免疫， 局部淋巴结、肠道和全身免疫反应。我们提出以下目标，以评估 未接种疫苗和接种疫苗的RM在用SIVmac 251攻击前和攻击后。目的1：研究先天性 目的2：研究适应性免疫 CD 4和CD 8 T细胞和B细胞的应答。待进行的研究将包括以下研究： 接种疫苗/病毒攻毒前、蚀食期和病毒攻毒后60天， 未接种疫苗的动物。包括宿主限制性因子Apobec 3G、病毒储库、 病毒多样化、NK细胞、γ-δ T细胞和适应性SIV特异性T和B细胞表型， 功能谱将在仔细协调和详尽的分析中确定， 蛋白质组学、组织病理学和免疫学分析，以深入了解宿主- SIV的相互作用和疫苗的相关性引起免疫保护。