Scientific Research Support Component C/Non- Human Primates

科学研究支持成分 C/非人类灵长类动物

• 批准号: 9089830
• 负责人: Dan H. Barouch
• 金额: $ 108.13万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9089830
• 关键词: AIDS/HIV problem; Affinity; Animal Model; Animals; Antibodies; Antigens; Autopsy; Basic Science; Blood specimen; CD4 Positive T Lymphocytes; Cells; Complex; Data Analyses; Data Collection; Development; Ensure; Goals; HIV-1; Helper-Inducer T-Lymphocyte; Human Resources; Immune response; Immunization; Immunologics; Immunology; Infection; Israel; Leadership; Macaca mulatta; Medical center; Mission; Monoclonal Antibodies; Positioning Attribute; Preclinical Testing; Primates; Procedures; Protocols documentation; Quality Control; Reagent; Research; Research Infrastructure; Research Personnel; Research Support; Resources; Role; SIV; Sampling; Technical Expertise; Testing; Tissue Sample; Universities; Vaccines; Walkers; Work; animal care; high standard; immunogenicity; in vivo; meetings; nonhuman primate; novel; programs; protective efficacy; research study; response; simian human immunodeficiency virus; success; virus characteristic

Infection of rhesus macaques with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) is a key animal model for HIV-1 infection. The Nonhuman Primate (NHP) Scientific Research Support Component (SRSC) aims to support this CHAVI-ID by providing all the expertise, infrastructure, reagents, personnel, and animals for the conduct of complex in vivo immunogenicity and challenge studies in NHPs. This SRSC will involve leadership from both Beth Israel Deaconess Medical Center and the Yerkes National Primate Research Center (Emory University) and is well positioned to meet the CHAVI-ID goals. This SRSC leadership will work closely with the research discovery teams responsible for the studies described in Scientific Foci #1 and#2 and participate actively in the scientific mission of this CHAVI-ID. The main role of this SRSC is to provide leadership and technical expertise to ensure consistency and quality control in animal selection, execution of study protocols, experimental procedures, sample acquisition and distribution, immunologic and virologic studies, and data collection and analysis. The Specific Aims are: 1. To support this CHAVI-ID by selecting and providing rhesus macaques, providing exceptional animal care, conducting experimental studies with monoclonal antibodies (MAbs) and vaccines, collecting samples for immunologic and virologic testing, and performing necropsy studies. These studies will initially evaluate: A. Protective efficacy of HIV-1 Env-specific MAbs against SHIV challenge; B. Immunogenicity and protective efficacy of novel HIV-1 Env immunogens and immunization strategies; 2. To support this CHAVI-ID by providing blood and tissue samples from SIV/SHIV-infected and uninfected NHPs to collaborating investigators to underpin basic research studies. These samples will support studies of neutralizing Abs in Focus #1 and will help elucidate the characteristics of virus-specific CD4+ follicular helper T cell (Tfh) responses in Focus #2, with an initial emphasis on the development of Tfh cells during vaccine-induced immune responses and the role of Tfh cells in promoting the affinity maturation of antibodies.

猴免疫缺陷病毒（SIV）或猴-人免疫缺陷病毒（SHIV）感染恒河猴是HIV-1感染的关键动物模型。非人灵长类动物（NHP）科学研究支持组件（SRSC）旨在通过提供所有专业知识、基础设施、试剂、人员和动物来支持该CHAVI-ID，以便在NHP中进行复杂的体内免疫原性和挑战研究。该SRSC将涉及来自Beth Israel Deaconess Medical Center和Yerkes National Primate Research Center（Emory University）的领导，并有能力实现CHAVI-ID的目标。 该SRSC领导层将与负责科学焦点#1和#2中所述研究的研究发现团队密切合作，并积极参与CHAVI-ID的科学使命。该SRSC的主要作用是提供领导和技术专业知识，以确保动物选择、研究方案执行、实验程序、样本采集和分发的一致性和质量控制，免疫学和病毒学研究以及数据收集和分析。具体目标是： 1.通过选择和提供恒河猴、提供特殊的动物护理、使用单克隆抗体（MAb）和疫苗进行实验研究、采集用于免疫学和病毒学检测的样本以及进行尸检研究，支持CHAVI-ID。这些研究将首先评估： A. HIV-1 Env特异性单克隆抗体对SHIV攻击的保护作用 B。新型HIV-1 Env免疫原的免疫原性、保护效果及免疫策略 2.通过向合作研究者提供SIV/SHIV感染和未感染NHP的血液和组织样本来支持CHAVI-ID，以支持基础研究。这些样本将支持焦点#1中中和抗体的研究，并将有助于阐明焦点#2中病毒特异性CD 4+滤泡辅助T细胞（Tfh）应答的特征，最初重点是疫苗诱导免疫应答期间Tfh细胞的发育以及Tfh细胞在促进抗体亲和力成熟中的作用。