Coronavirus Challenge Core

冠状病毒挑战核心

• 批准号: 10420513
• 负责人: Matthew Bryan Frieman
• 金额: $ 144.15万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 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/10420513
• 关键词: 2019-nCoV; ACE2; Adenovirus Vector; Animal Model; Animals; Antibodies; Antibody Response; Attenuated Live Virus Vaccine; B-Lymphocytes; Binding; Biological Assay; Body Weight decreased; Cell Line; Cells; Chiroptera; Coronavirus; Development; Dose; Engineering; Ensure; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation; Flow Cytometry; Goals; Hamsters; Human; Immune; Immune Sera; Immunity; Immunize; Immunologics; Individual; Inflammation; Infrastructure; Laboratories; Merbecovirus; Mesocricetus auratus; Methods; Middle East Respiratory Syndrome Coronavirus; Mus; Pan Genus; Pathologic; Pathology; Peripheral Blood Mononuclear Cell; Program Research Project Grants; Proteins; Research; Rodent Model; SARS coronavirus; Sarbecovirus; Serum; Spleen; Surface; T cell response; T-Lymphocyte; Testing; Transgenic Mice; Transgenic Organisms; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Vesicular stomatitis Indiana virus; Viral; Viral load measurement; Virus; animal coronavirus; base; betacoronavirus; cross immunity; cross reactivity; data management; design; experimental study; human coronavirus; immunogenicity; pandemic disease; pre-clinical; protective efficacy; receptor; receptor binding; universal coronavirus vaccine; vaccine candidate; vaccine efficacy; vaccine evaluation

Project Summary – Animal Challenge Core B The Animal Challenge Core B will develop and provide key virus stocks for four different human and animal coronaviruses (CoVs) that have pandemic potential. These viruses belong to the subgenera of Sarbecovirus and Merbecovirus and will be used by the Core for challenge studies in mice and Syrian hamsters to evaluate cross-protective efficacy of vaccines against diverse betacoronaviruses. The virus stocks, generated by Core B, also will be used in virus neutralization assays prior to challenge or after immunogenicity testing of vaccines in mice and hamsters. The specific functions of Core B will include: (a) generating validated stocks of four different betacoronaviruses including SARS-CoV-1, SARS-CoV-2, SHC-014 and pangolin/MP789/2019; (b) developing rodent models for bat coronaviruses; (c) Contributing to and performing pivotal immunogenicity studies in mice and hamsters to quantify the B and T cell response to vaccination with different vaccine candidates generated in Projects 1-3; (d) Performing virus challenge studies with human and bat CoV in mice and hamsters immunized with candidate vaccines that induce broadly reactive B- and T-cell responses to diverse betacoronaviruses. The results from Core B will be used by the data management team in Core A to identify correlates of immune cross-protection against betacoronaviruses of pandemic concern. These functons will enable the PPG group to determine whether a candidate vaccine induces broadly protective immunity against human and animal CoV. This Core B, led by Drs. Frieman and Boon, will meet the needs of the PPG by acquiring and generating challenge viruses, developing animal models and performing immunogenicity and vaccine challenges studies in established rodent models of betacoronaviruses. These functions provide key infrastructure support for all research projects of the PPG.

项目摘要-动物挑战核心B 动物挑战核心B将为四个不同的人类开发和提供关键病毒储备 以及具有大流行潜力的动物冠状病毒(CoV)。这些病毒属于 沙贝病毒亚属和沙贝病毒亚属，并将被核心用于挑战研究 在小鼠和叙利亚仓鼠中评估疫苗对不同病毒的交叉保护效果 贝塔冠状病毒。核心B产生的病毒库存也将用于病毒中和 在小鼠和仓鼠中进行疫苗免疫原性测试之前或之后的化验。这个 核心B的具体功能将包括：(A)生成四种不同的有效库存 贝塔冠状病毒包括SARS-CoV-1、SARS-CoV-2、SHC-014和穿山甲/MP789/2019； (B)建立蝙蝠冠状病毒的啮齿动物模型；(C)促进和发挥关键作用 用小鼠和仓鼠进行免疫原性研究以量化B和T细胞对疫苗接种的反应 在项目1-3中产生不同的候选疫苗；(D)进行病毒挑战 人和蝙蝠冠状病毒在小鼠和仓鼠中的研究 诱导广泛反应的B细胞和T细胞对不同的贝塔冠状病毒的反应。结果来自于 核心A的数据管理团队将使用核心B来确定免疫的关联性 对引起大流行关注的贝塔冠状病毒的交叉保护。这些功能将使 PPG小组确定候选疫苗是否能诱导广泛的保护性免疫 对抗人类和动物的冠状病毒。这个由Frieman博士和Boon博士领导的核心B将满足需求 通过获取和产生挑战病毒，开发动物模型和 在已建立的鼠类模型中进行免疫原性和疫苗挑战研究 贝塔冠状病毒。这些功能为所有研究项目提供关键的基础设施支持 PPG。