Scientific Core: BSL3 Virology and Animal Models

科学核心：BSL3 病毒学和动物模型

基本信息

批准号：
10327991
负责人：
Charles M Rice
金额：
$ 145.45万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
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/10327991
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 base design efficacy testing expectation experience experimental study human coronavirus human model in vivo neutralizing antibody novel novel coronavirus pandemic coronavirus pandemic disease particle programs response universal coronavirus vaccine vaccination strategy vaccine candidate vaccine development virology

项目摘要

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共同19-19大流行破坏了全球社会的各个方面。这个总体主题 P01提案是研究以SARS-COV-2感染的免疫回报及其对其他的反应性冠状病毒（COVS）使得导致广泛中和活动的免疫策略可以通过开发一种疫苗的最终目标，该疫苗将为可能的未来新兴COV提供保护。 BSL3病毒学和动物模型核心（Charles Rice/Margaret MacDonald）的目标将产生试剂并开发和执行测定，以支持三个研究项目的目标博士。 Michel Nussenzweig和Marina Caskey（项目1），博士。 Paul Bieniasz和Theodora Hatziioannou （项目2）和Pamela Bjorkman博士（项目3）。这三个项目，病毒学和动物模型核心和行政核心旨在实现该计划的目标的目标 SARS-COV-2感染或接种疫苗的个体的免疫力，以定义任何针对的构成表位中和抗体，以研究结构和功能方法中和的机制，并在小动物模型中进行测试，旨在引起最大中和的抗体宽度。为了满足程序目标，将采用分子病毒学，细胞培养和动物模型方法由BSL3病毒学和动物模型核心在四个目标中1）开发用于体外和的COV工作库存体内使用（项目1、2和3），2）开发用于测试血清神经元化活性并克隆的简便系统使用包含跨包装的复制剂（TPR）的抗体，带有广泛COV的尖峰蛋白，包括潜在的大流行关注的人（项目2和3），3）对SARS进行体外谈判测定法 COV-2和其他COVS或TPR使用人类和动物的最佳候选血清和克隆的抗体所有三个项目的模型和4）小动物模型中的性能免疫和保护实验测试候选单克隆抗体和疫苗接种策略的效率。总体而言，工作将为可以用来减轻威胁的pan-cov疫苗的开发做出了重大贡献未来的cov pandemics。