Project 1: Immune Memory

项目一：免疫记忆

• 批准号: 10394365
• 负责人: Rafi Ahmed
• 金额: $ 251.68万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-02 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394365
• 关键词: 2019-nCoV; Acute; Adult; Antibodies; Antibody Response; B-Lymphocytes; Binding; Biological Assay; Cells; Clinic; Convalescence; Coronavirus; Development; Diagnostic; Disease; Elderly; Emerging Communicable Diseases; Gene Expression Profile; Goals; Health Personnel; Human; Humoral Immunities; Immune response; Immunologic Memory; Infection; Peripheral Blood Mononuclear Cell; Protocols documentation; SARS-CoV-2 antibody; SARS-CoV-2 infection; Sampling; Serology; Serology test; Serum; Source; Testing; Therapeutic; University Hospitals; Urban Hospitals; Vaccines; Viral; Virus; Virus Diseases; acute infection; adaptive immune response; aged; biosafety level 3 facility; expression cloning; human monoclonal antibodies; insight; instrument; response; seroconversion; serosurveillance; tool; vaccine-induced immunity

The over-arching goal of this proposal is to analyze SARS-CoV-2 antibody seroconversion rates in health care workers at the Emory University Hospital over the next year and to study adaptive immune responses to SARS-CoV-2 infection during acute infection and at convalescence. These studies will draw on three main sources of samples, either through an emerging infectious disease protocol at the Emory Vaccine Center Hope Clinic, through a sero-surveillance study initiated at Emory, and previously collected PBMC and serum samples from adult or elderly donors by Dr. Jorg Goronzy, respectively. We will develop and employ a combination of antibody binding assays and viral neutralization assays to test the quantity and quality of the infection-induced antibody responses. This information will also be used to identify optimal donors for single-cell antibody expression cloning, as we have previously described9-13. A recently purchased 10x instrument in our BSL3 facility at the Emory Vaccine Center will allow for a detailed analysis of the transcriptional profiles of innate and adaptive immune responses during acute SARS-CoV-2 infection. The proposed studies will provide key insight into the dynamics of this devastating disease among health care workers at a major metropolitan hospital in Atlanta. These efforts will also generate key serological tools, provide an understanding of the humoral immune response to SARS-CoV-2 infection, and generate human monoclonal antibodies, with both diagnostic and therapeutic potential.

该提案的首要目标是分析健康人群中的 SARS-CoV-2 抗体血清转化率 埃默里大学医院的护理人员明年将研究适应性免疫反应 急性感染期间和恢复期的 SARS-CoV-2 感染。这些研究将借鉴三个 样本的主要来源，要么通过埃默里疫苗局的新发传染病方案 Center Hope Clinic，通过埃默里大学发起的一项血清监测研究，之前收集了 PBMC 以及 Jorg Goronzy 博士分别采集的成人或老年捐献者的血清样本。我们将开发和 采用抗体结合测定和病毒中和测定的组合来测试数量和 感染引起的抗体反应的质量。该信息还将用于确定最佳 正如我们之前所描述的9-13，单细胞抗体表达克隆的供体。最近一个 在埃默里疫苗中心的 BSL3 设施中购买的 10 倍仪器将可以进行详细分析 急性 SARS-CoV-2 期间先天性和适应性免疫反应的转录谱 感染。拟议的研究将为了解这种毁灭性疾病的动态提供重要见解 亚特兰大一家大都会医院的医护人员。这些努力也将产生关键 血清学工具，提供对 SARS-CoV-2 感染的体液免疫反应的了解， 并产生具有诊断和治疗潜力的人类单克隆抗体。