Core B: Non-Human Primate Core

核心 B：非人类灵长类核心

• 批准号: 10723637
• 负责人: Michael K Axthelm
• 金额: $ 43.77万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723637
• 关键词: Action Research; Animal Housing; Animal Model; Animals; Autopsy; Blood; Cells; Clinical; Clinical Data; Clinical Management; Communicable Diseases; Complex; Data; Data Analyses; Data Collection; Dependence; Discipline; Elements; Ensure; Event; Generations; Goals; HIV-1; Human; Human Resources; Immune response; Immunity; Immunize; Immunologics; Infection; Infrastructure; Interleukin-15; Investigation; Lead; Leadership; Link; Lymphoid Tissue; Macaca mulatta; Mission; Modeling; Mucous Membrane; Pathologic; Performance; Peripheral; Persons; Physiological; Procedures; Program Research Project Grants; Protocols documentation; Quality Control; Records; Research; Research Personnel; Risk; Role; SIV; SIV Vaccines; Safety; Sampling; Signal Pathway; Signal Transduction; Specimen Handling; Structure; Supervision; System; Technical Expertise; Tissues; Vaccination; Vaccines; Virus Diseases; Whole Blood; Work; design; experience; experimental study; nonhuman primate; novel; programs; response; sample collection; simian human immunodeficiency virus; transcriptomics; vaccine efficacy; vaccine response; vector; virtual

NHP CORE B SUMMARY The Nonhuman Primate (NHP) Core seeks to consolidate supervision and performance of the NHP experimental protocols of the Program Project entitled “Mechanisms Programming Protective Immunity from RhCMV/SIV Vaccine and IL-15 Actions” into a structured Core composed of highly experienced research personnel. The global objective of the Core is to provide leadership and technical expertise to ensure consistency and quality control in animal selection, execution of study protocols, application of experimental procedures, animal observations and data collection necessary to meet the objectives of Project and other Core lead investigators. To accomplish this, the Core will manage and directly supervise all NHP studies for the Project including: 1) animal selection; 2) animal housing and general husbandry; 3) experimental procedures and clinical management; 4) specimen collection and processing; 5) necropsy studies; and 6) acquisition and management of animal demographic, physiologic, clinical, and pathologic data. The overall objective of the Program Project is to determine the systems response to RhCMV/SIV vaccination and the role of IL-15 signaling in programming vaccine-induced immune responses responsible for complete arrest and subsequent clearance of SIV infection in RhCMV/SIV-immunized rhesus macaques. The NHP Core will provide the expertise and technical support required to ensure successful completion of the six multifaceted and extensive NHP experimental protocols supporting the 2 projects proposed in this Program. These studies are designed to: a) determine systemic transcriptomic correlates of the RhCMV/SIV vaccine-induced whole blood Protection-Predictive Transcriptomic Signature [wbPPTS] in peripheral and mucosal lymphoid tissues and its dependence on IL-15 signaling (Project 1); b) define specific spatial transcriptomic response to RhCMV/SIV-infected cells in tissues and identify the direct contribution of vector-infected cells to the local and systemic transcriptomic responses linked to wbPPTS programming (Project 1); c) determine the mechanisms underlying the association between IL-15 signaling quiescence and generation of the wbPPTS (Project 1) and d) link the tissue and blood transcriptomic programming identified is a-c to IL-15 signaling pathways, RhCMV/SIV vaccine efficacy and the larger vaccine response landscape in NHP and people (Project 2).

NHP核心B摘要 非人类灵长类动物（NHP）核心旨在巩固NHP实验的监督和绩效 标题为“RhCMV/SIV保护性免疫机制”的计划项目方案 疫苗和IL-15行动”纳入一个由经验丰富的研究人员组成的结构化核心。的 核心的全球目标是提供领导和技术专长，以确保一致性和质量 动物选择的控制、研究方案的执行、实验程序的应用、动物 为实现项目和其他核心主要研究者的目标所需的观察和数据收集。 为实现这一目标，核心委员会将管理并直接监督项目的所有NHP研究，包括：1） 动物选择; 2）动物圈养和一般饲养; 3）实验程序和临床 管理; 4）标本采集和处理; 5）尸检研究;以及6）采集和管理 动物的人口统计学、生理学、临床和病理学数据。计划项目的总体目标 确定RhCMV/SIV疫苗接种的系统应答以及IL-15信号在编程中的作用 疫苗诱导的免疫应答负责完全阻止和随后清除SIV感染 在RhCMV/SIV免疫的恒河猴中。NHP核心将提供专业知识和技术支持 确保成功完成六个多方面和广泛的NHP实验方案 支持本计划中提出的2个项目。这些研究旨在：a）确定系统性 RhCMV/SIV疫苗诱导的全血保护作用的转录组学相关性-预测性转录组学 外周和粘膜淋巴组织中的签名[wbPPTS]及其对IL-15信号传导的依赖性（项目 1）; B）定义组织中对RhCMV/SIV感染的细胞的特异性空间转录组学应答，并鉴定 载体感染细胞对与wbPPTS相关的局部和全身转录组学应答的直接贡献 c）确定IL-15信号传导与IL-12信号传导之间的关联的潜在机制; wbPPTS的静止和产生（项目1）和d）将组织和血液转录组学连接起来， 编程确定的是a-c到IL-15的信号通路，RhCMV/SIV疫苗的功效和较大的疫苗 国家卫生方案和人的应对景观（项目2）。