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 概要 非人类灵长类动物 (NHP) 核心旨在巩固 NHP 实验的监督和绩效 题为“RhCMV/SIV 保护性免疫编程机制”的计划项目协议 疫苗和 IL-15 行动”纳入由经验丰富的研究人员组成的结构化核心。 核心的全球目标是提供领导力和技术专业知识，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首席研究员的目标所必需的观察和数据收集。 为了实现这一目标，核心将管理和直接监督该项目的所有 NHP 研究，包括：1) 动物选择； 2）动物饲养和一般畜牧业； 3）实验程序和临床 管理; 4）标本采集和处理； 5）尸检研究； 6) 收购和管理 动物人口统计、生理、临床和病理数据。计划项目的总体目标 目的是确定系统对 RhCMV/SIV 疫苗接种的反应以及 IL-15 信号在编程中的作用 疫苗诱导的免疫反应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 实验方案所需 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预测转录组学的转录组学相关性 外周和粘膜淋巴组织中的特征 [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 感染细胞的特定空间转录组反应，并确定 载体感染细胞对与 wbPPTS 相关的局部和全身转录组反应的直接贡献 编程（项目1）； c) 确定IL-15信号传导之间关联的潜在机制 wbPPTS 的静止和生成（项目 1）和 d) 将组织和血液转录组联系起来 确定的程序是 IL-15 信号通路、RhCMV/SIV 疫苗功效和更大的疫苗 NHP 和人类的响应情况（项目 2）。