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.

项目摘要 - 核心B：病毒学人畜共努性冠状病毒（COV）负责21世纪的三个主要流行病/大流行病，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）2012年。2019年12月，第三本小说的冠状病毒指定了SARS-COV-2在中国武汉出现在18个月的空间中，造成超过1.7亿例和3,500,000例死亡人数220多人国家。在美国，大约有六分之一的案件报告，导致超过60万人死亡。令人担忧的是，蝙蝠和其他物种都存在多种不同的类似SARS和类似MERS的COV菌株，并且准备在将来出现，从而产生对广泛保护的疫苗的批判性需求。我们试图发展一个 Pan-Betacoronavirus疫苗将普遍预防SARBECOVIRUS，MERBECOVIRUS，MERBECOVIRUS，和Embecovirus子属。核心B（病毒学，Baric）的目标是：i）提供组SARBECOVIRUS， Merbecovirus和人类疾病的Embecovirus动物模型，用于评估疫苗性能； ii）开发反向遗传平台，重组病毒和动物模型为其他高风险人畜共患病冠状病毒; iii）评估不断扩展的SARS-COV-22大流行中的病毒进化并创造适当的在体内评估泛甲苯甲状腺癌疫苗性能的试剂； iv）评估机制同源后（即疫苗应变）和异源后的调节保护性或致病性免疫反应挑战。总体目标是识别高性能的泛 - 萨尔贝病毒和pan-betacoronavirus疫苗在至少两个动物模型中提供强大保护的免疫反应的候选者。