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Core B: Virology Core

核心 B：病毒学核心

基本信息

批准号：
10425027
负责人：
Ralph S Baric
金额：
$ 215.31万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2022-09-02 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10425027
关键词：
2019-nCoV Acute Respiratory Distress Syndrome Adverse reactions Animal Model Antibodies Biological Assay Blood Coagulation Disorders COVID-19 Cessation of life China Chiroptera Clinical Collaborations Coronavirus Country Data Disease Distant Ensure Epidemic Epitopes Evolution Future Generations Goals Human Immune Immune Sera Immune System Diseases Immune response Immunity Immunotherapeutic agent Infection Laboratories Leukocytes Maps Merbecovirus Middle East Middle East Respiratory Syndrome Middle East Respiratory Syndrome Coronavirus Mus Outcome Pathogenesis Pathogenicity Performance Pneumonia Primates Production Program Research Project Grants Reagent Recombinants Reporting Respiratory physiology SARS coronavirus SARS-CoV-2 B.1.1.7 SARS-CoV-2 B.1.351 Sampling Sarbecovirus Serum Severe Acute Respiratory Syndrome Shock Stroke Structure Syndrome Talents Tropism Vaccine Design Vaccines Variant Viral Virulent Virus Zoonoses aged animal coronavirus animal model development base betacoronavirus betacoronavirus vaccine comparative coronavirus vaccine cytokine design high risk human disease human model in vivo model development mouse model nanoluciferase nanoparticle neutralizing antibody nonhuman primate novel novel coronavirus pandemic disease programs recombinant virus recruit respiratory response reverse genetics structural biology universal vaccine vaccine candidate vaccine evaluation vaccine platform vaccine response vaccine-induced antibodies vaccinology variants of concern virology zoonotic coronavirus

项目摘要

PROJECT SUMMARY – CORE B: VIROLOGY Zoonotic coronaviruses (CoV) are responsible for three major epidemics/pandemics in the 21st century, including Severe Acute Respiratory Coronavirus (SARS-CoV) in 2003 and Middle East Respiratory coronavirus (MERS- CoV) in 2012. In December 2019 a third novel coronavirus designated SARS-CoV-2 emerged in Wuhan China, and in the space of 18 months has caused over 170 million cases and 3,500,000 deaths in more than 220 countries. About one-sixth of these total cases have been reported in the US, resulting in over 600,000 deaths. Of concern, multiple distinct SARS-like and MERS-like CoV strains reside in bats and other species and are poised to emerge in the future, creating a critical need for broadly protective vaccines. We seek to develop a pan-betacoronavirus vaccine that will universally protect against viruses from the sarbecovirus, merbecovirus, and embecovirus subgenera. The goals of Core B (Virology, Baric) are to: i) provide group sarbecovirus, merbecovirus, and embecovirus animal models of human disease for evaluating vaccine performance; ii) develop reverse genetic platforms, recombinant viruses, and animal models to other high risk zoonotic coronaviruses; iii) evaluate virus evolution in the expanding SARS-CoV-22 pandemic and create appropriate reagents to evaluate pan-betacoronavirus vaccine performance in vivo; and iv) evaluate the mechanisms regulating protective or pathogenic immune responses after homologous (i.e., vaccine-strain) and heterologous challenge. The overall goal is to identify high-performance pan-sarbecovirus and pan-betacoronavirus vaccine candidates that provide robust protective immune responses in at least two animal models.

项目总结-核心B：病毒学人畜共患冠状病毒（CoV）是21世纪三大流行病/大流行病的罪魁祸首，包括 2003年的严重急性呼吸道冠状病毒（SARS-CoV）和中东呼吸道冠状病毒（MERS- CoV）在2012年。2019年12月，第三种新型冠状病毒SARS-CoV-2在中国武汉出现，在18个月的时间里，在220多个国家，国家这些病例中约有六分之一发生在美国，导致60多万人死亡。值得关注的是，多种不同的SARS样和MERS样CoV毒株存在于蝙蝠和其他物种中，这些疾病在未来可能会出现，这就迫切需要具有广泛保护性的疫苗。我们致力发展一个泛β冠状病毒疫苗，将普遍保护免受病毒从肉瘤病毒，梅贝科病毒，和恩贝可病毒亚属。核心B（病毒学，Baric）的目标是：i）提供组肉瘤病毒，用于评估疫苗性能的人类疾病的猴病毒和恩贝病毒动物模型; ii）开发反向遗传平台，重组病毒和动物模型，以其他高风险的人畜共患病 iii）评估病毒在扩大的SARS-CoV-22大流行中的演变，并创建适当的评估泛β冠状病毒疫苗体内性能的试剂;和iv）评估机制在同源（即，疫苗株）和异源挑战.总体目标是确定高性能泛肉瘤病毒和泛β冠状病毒疫苗在至少两种动物模型中提供稳健的保护性免疫应答的候选物。