Scientific Core: BSL3 Virology and Animal Models

科学核心：BSL3 病毒学和动物模型

• 批准号: 10841239
• 负责人: Charles M Rice
• 金额: $ 98.31万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-03 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10841239
• 关键词: 2019-nCoV; ACE2; Animal Model; Antibodies; Antibody Response; Antigens; Biological Assay; COVID-19 pandemic; Cell Culture Techniques; Chiroptera; Containment; Coronavirus; Coronavirus spike protein; Development; Epitopes; Future; Goals; Human; Immune response; Immunity; Immunization; Immunize; In Vitro; Infection; Knowledge; Luciferases; Measures; Mesocricetus auratus; Modeling; Molecular Virology; Monoclonal Antibodies; Mus; Neutralization Tests; New York City; Proteins; Reagent; Replicon; Research Personnel; Research Project Grants; Rice; Role; Serology; Societies; System; Testing; Transgenic Organisms; Vaccinated; Vaccinee; Virus; Work; coronavirus pandemic; design; efficacy testing; expectation; experience; experimental study; human coronavirus; human model; in vivo; neutralizing antibody; novel; novel coronavirus; pandemic coronavirus; pandemic potential; particle; programs; response; universal coronavirus vaccine; vaccination strategy; vaccine candidate; vaccine development; virology

Project Summary – BSL3 Virology and Animal Models Core The COVID-19 pandemic has disrupted all aspects of society across the globe. The overarching theme of this P01 proposal is to study immune responses to infection with SARS-CoV-2 and their reactivity against other coronaviruses (CoVs) such that immunization strategies resulting in broad neutralizing activity can be tested with the ultimate goal of developing a vaccine that will provide protection against likely future emerging CoVs. The goals of the BSL3 Virology and Animal Models Core (Charles Rice/Margaret MacDonald) are to generate reagents and develop and perform assays in support of the objectives of three Research Projects, headed by Drs. Michel Nussenzweig and Marina Caskey (Project 1), Drs. Paul Bieniasz and Theodora Hatziioannou (Project 2) and Dr. Pamela Bjorkman (Project 3). Together the three Projects, the Virology and Animal Models Core and the Administrative Core aim to accomplish the Program's goal of defining the breadth of serological immunity in SARS-CoV-2 infected or vaccinated individuals, to define any conserved epitopes targeted by neutralizing antibodies, to investigate mechanisms of neutralization using structural and functional approaches, and to test in small animal models immunogens designed to elicit antibodies with maximum neutralization breadth. To meet the program goals, molecular virology, cell culture and animal model approaches will be taken by the BSL3 Virology and Animal Models Core in four Aims to 1) develop CoV working stocks for in vitro and in vivo use (Projects 1, 2 and 3), 2) develop facile systems for testing the neutralization activity of sera and cloned antibodies using trans-packaged replicons (TPRs) bearing the spike proteins of a broad range of CoVs, including those of potential pandemic concern (Projects 2 and 3), 3) conduct in vitro neutralization assays against SARS- CoV-2 and other CoVs or TPRs using the best candidate sera and cloned antibodies from humans and animal models from all three Projects and 4) perform immunization and protection experiments in small animal models to test the efficacy of candidate monoclonal antibodies and vaccination strategies. Overall, the work will contribute significantly to the development of pan-CoV vaccine candidates that can be used to mitigate the threat of future CoV pandemics.

项目摘要 – BSL3 病毒学和动物模型核心 COVID-19 大流行扰乱了全球社会的各个方面。本次活动的总体主题是 P01提案是研究对SARS-CoV-2感染的免疫反应及其对其他病毒的反应 冠状病毒（CoV），因此可以测试产生广泛中和活性的免疫策略 最终目标是开发一种能够针对未来可能出现的冠状病毒提供保护的疫苗。这 BSL3 病毒学和动物模型核心（Charles Rice/Margaret MacDonald）的目标是生成 试剂并开发和执行分析，以支持三个研究项目的目标，这些项目由 博士。 Michel Nussenzweig 和 Marina Caskey（项目 1），博士。保罗·比尼亚斯和西奥多拉·哈齐约安努 （项目 2）和 Pamela Bjorkman 博士（项目 3）。这三个项目、病毒学和动物模型一起 核心和管理核心旨在实现该计划的目标，即定义血清学的广度 SARS-CoV-2 感染或接种疫苗的个体的免疫力，以确定任何保守的表位 中和抗体，使用结构和功能方法研究中和机制， 并在小动物模型中测试旨在引发最大中和抗体的免疫原 宽度。为了实现计划目标，将采用分子病毒学、细胞培养和动物模型方法 BSL3 病毒学和动物模型核心的四个目标是 1) 开发用于体外和 体内使用（项目 1、2 和 3），2) 开发用于测试血清和克隆的中和活性的简便系统 使用带有多种 CoV 刺突蛋白的反式包装复制子 (TPR) 的抗体，包括 那些潜在的大流行问题（项目2和3），3）针对SARS进行体外中和试验 使用来自人类和动物的最佳候选血清和克隆抗体检测 CoV-2 和其他 CoV 或 TPR 来自所有三个项目的模型和 4) 在小动物模型中进行免疫和保护实验 测试候选单克隆抗体和疫苗接种策略的功效。总体而言，这项工作将 为开发可用于减轻威胁的泛冠状病毒候选疫苗做出重大贡献 未来的冠状病毒大流行。