Scientific Core: BSL3 Virology and Animal Models

项目摘要-BSL3病毒学和动物模型核心 新冠肺炎大流行已经扰乱了全球社会的方方面面。这件事的主要主题是 P01建议研究感染SARS-CoV-2的免疫反应及其对其他病毒的反应性 冠状病毒(CoV)的免疫策略可以产生广泛的中和活性，可以用 开发一种疫苗的最终目标是提供对未来可能出现的冠状病毒的保护。这个 BSL3病毒学和动物模型核心(查尔斯·赖斯/玛格丽特·麦克唐纳)的目标是产生 为支持三个研究项目的目标而开发和执行分析试剂，该项目由 Michel Nussenzweig博士和Marina Caskey博士(项目1)、Paul Bieniasz博士和Theodora HatziioAnnou博士 (项目2)和帕梅拉·比约克曼博士(项目3)。三个项目一起，病毒学和动物模型 核心和管理核心旨在实现项目确定血清学广度的目标 在感染或接种SARS-CoV-2的个体中的免疫力，以确定靶向的任何保守表位 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免疫原，旨在最大限度地中和产生抗体 广度。为了实现计划目标，将采取分子病毒学、细胞培养和动物模型方法。 由BSL3病毒学和动物模型核心中的四个目标1)开发体外和 体内应用(项目1、2和3)，2)开发用于检测血清和克隆的血清中和活性的简易系统 使用携带多种冠状病毒尖峰蛋白的反式包装复制子(TPR)的抗体，包括 那些可能引起大流行的项目(项目2和项目3)，3)进行针对SARS的体外中和试验- 使用来自人和动物的最佳候选血清和克隆抗体的CoV-2和其他CoV或TPR 所有三个项目的模型和4)在小动物模型上进行免疫和保护实验 测试候选单抗和疫苗接种策略的效果。总的来说，这项工作将 为开发可用于缓解威胁的泛冠状病毒候选疫苗做出重大贡献 未来冠状病毒大流行的可能性。

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.