Coronavirus neutralizing antibody epitopes and immunogens

冠状病毒中和抗体表位和免疫原

基本信息

批准号：
10841241
负责人：
Paul D. Bieniasz
金额：
$ 98.31万
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/10841241
关键词：
2019-nCoV Address Affect Animal Experiments Animal Model Animals Antibodies Antigens Appearance COVID-19 pandemic COVID-19 treatment Chiroptera Coronavirus Development Effectiveness Engineering Epitopes Future Genes Glycoproteins Goals HIV-1 Half-Life Health Human Humanities IgG1 Individual Infection Knowledge Location Maps Methods Middle East Respiratory Syndrome Coronavirus Molecular Conformation Monoclonal Antibodies Mucous Membrane Mutation Participant Plasma Population Process Production Protein Array Proteins Readiness Recurrence Resistance SARS coronavirus SARS-CoV-2 infection SARS-CoV-2 spike protein Serum Site Somatic Mutation Speed Study models System Testing Time Uncertainty Vaccine Antigen Vaccinee Vaccines Variant Vesicular stomatitis Indiana virus Virus Zoonoses adeno-associated viral vector animal coronavirus combat convalescent plasma coronavirus pandemic design experience experimental study future pandemic improved in vivo evaluation mutant neutralizing antibody neutralizing monoclonal antibodies nonhuman primate novel novel coronavirus pandemic coronavirus preservation prevent programs success tool vaccination strategy vaccine development vector zoonotic coronavirus

项目摘要

ABSTRACT-PROJECT 2 The SARS-CoV-2 pandemic has established beyond doubt that animal coronaviruses are a major potential threat to human health. Although vaccines and antibodies to prevent and treat SARS-CoV-2 infection have been developed at unprecedented speed, the recurrent emergence of coronaviruses from bat and other animal reservoirs underlines the need for preparedness to prevent future pandemics. Current vaccines have been designed to combat SARS-CoV-2, but it is unclear how effective they will be in the future against emergent variants in circulating SARS-CoV-2 populations and, importantly, against other potentially zoonotic coronaviruses. To generate immunogens that can elicit broad neutralizing antibodies targeting multiple, distinct coronaviruses we need first to understand what epitopes on the coronavirus envelope glycoprotein spike constitute targets for neutralizing antibodies. Therefore, the first aim of this project will be to deploy an array of VSV-based and HIV-1 based pseudotyped and viruses to identify SARS-CoV-2 epitopes targeted by human neutralizing antibodies found in SARS-CoV-2 convalescent or vaccinee plasma. Additionally, we will determine to what extent these epitopes are functionally preserved in progressively more divergent coronaviruses. In the second aim, we will use this and other information to design immunogens and immunization strategies. We will employ a variety of multivalent immunogens and delivery methods aimed to prolong antigen exposure and maximize antibody somatic mutation. The goal of these experiments will be to elicit production of neutralizing antibodies with the maximum possible breadth, and test their ability to protect against infection by pandemic threat coronaviruses.

摘要-项目 2 SARS-CoV-2 大流行毫无疑问地证明动物冠状病毒是对人类健康的主要潜在威胁。尽管用于预防和治疗 SARS-CoV-2 感染的疫苗和抗体已经以前所未有的速度开发出来，但蝙蝠和其他动物宿主中反复出现的冠状病毒凸显了做好准备以预防未来大流行的必要性。目前的疫苗是为了对抗 SARS-CoV-2 而设计的，但目前尚不清楚它们未来对流行的 SARS-CoV-2 群体中的新变种，尤其是对其他潜在人畜共患冠状病毒的有效性如何。为了产生能够引发针对多种不同冠状病毒的广泛中和抗体的免疫原，我们首先需要了解冠状病毒包膜糖蛋白刺突上的哪些表位构成中和抗体的目标。因此，该项目的首要目标是部署一系列基于 VSV 和 HIV-1 的假型病毒和病毒，以识别 SARS-CoV-2 恢复期或疫苗接种者血浆中发现的人类中和抗体所针对的 SARS-CoV-2 表位。此外，我们将确定这些表位在逐渐多样化的冠状病毒中功能保留的程度。在第二个目标中，我们将利用这些信息和其他信息来设计免疫原和免疫策略。我们将采用多种多价免疫原和递送方法，旨在延长抗原暴露并最大化抗体体细胞突变。这些实验的目标是引发尽可能广泛的中和抗体的产生，并测试它们抵御大流行威胁冠状病毒感染的能力。