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SARS-CoV-2抗体血清转换率 在接下来的一年里，埃默里大学医院的护理人员，并研究适应性免疫反应 SARS-CoV-2感染的急性期和恢复期。这些研究将借鉴三个 样本的主要来源，无论是通过埃默里疫苗的新兴传染病协议， Center Hope Clinic，通过在Emory启动的血清监测研究， 和血清样本，分别来自成人或老年供体，由Jorg Goronzy博士。创新和 采用抗体结合测定和病毒中和测定的组合来测试所述量， 感染诱导的抗体应答的质量。这些信息还将用于确定最佳的 供体用于单细胞抗体表达克隆，如我们先前所述9 -13。一个最近 在我们位于埃默里疫苗中心的BSL 3设施中购买的10倍仪器将允许进行详细分析 急性SARS-CoV-2期间先天性和适应性免疫应答的转录谱 感染拟议中的研究将为这种毁灭性疾病的动态提供关键的见解 在亚特兰大一家大都市医院的医护人员中。这些努力也将产生关键的 血清学工具，提供了对SARS-CoV-2感染的体液免疫反应的理解， 并产生具有诊断和治疗潜力的人单克隆抗体。