Project 1: Serology

项目1：血清学

• 批准号: 10222105
• 负责人: Taia Wang
• 金额: $ 93.14万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-23 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222105
• 关键词: 2019-nCoV; Alanine; Amino Acids; Antibodies; Antibody Response; Antibody Specificity; Antigen Targeting; Antigen-Antibody Complex; B-Lymphocytes; Binding; COVID-19; Cell Line; Characteristics; Clinical; Clonal Expansion; Collaborations; Cryoelectron Microscopy; Demographic Factors; Development; Disease; Dissection; Engineering; Epitope Mapping; Epitopes; Escape Mutant; Evaluation; Genetic; Health; Heterogeneity; Human; Humoral Immunities; IgG Receptors; Immunity; Immunoglobulin-Secreting Cells; Infection; Inflammation; Joints; Kinetics; Life; Maps; Mediating; Membrane Proteins; Memory; Memory B-Lymphocyte; Methods; Molecular; Monoclonal Antibodies; Mucous Membrane; Mutate; Outcome; Pathogenesis; Patients; Phenotype; Play; Pneumonia; Population; Prevention; Property; Proteins; RNA Viruses; Research; Research Personnel; Resolution; Role; Sampling; Sampling Studies; Serologic tests; Serological; Sorting - Cell Movement; Specificity; Structure; Symptoms; T-Lymphocyte; Testing; Therapeutic Monoclonal Antibodies; Therapeutic antibodies; Vaccine Adjuvant; Vaccine Design; Vaccines; Viral Antigens; Viral Proteins; Virion; Virus; Virus Diseases; Work; clinically significant; cytokine; design; mutant; novel vaccines; pandemic disease; passive antibodies; pathogen; reconstitution; response; seropositive; tool; trend; vaccine efficacy

PROJECT 1: SUMMARY As established through decades of research in protective immunity against infectious pathogens, achieving durable immunity against SARS-CoV-2 will require specific functional properties of antibodies, B cells and T cells that need to be defined through detailed repertoire studies. Antibody responses to viral infections in humans are varied and of widely divergent clinical significance. Pre-existing, reactive antibodies or antibodies that are formed early during infection can engage virus particles, forming immune complexes that may neutralize or mediate clearance of the virus. On the other hand, immune complexes can also promote inflammation and exacerbate symptoms of disease. SARS-CoV-2 infections can be asymptomatic or cause disease, COVID-19, which manifests with a spectrum of symptoms ranging from mild to life threatening pneumonia and cytokine dysregulation. The role of antibodies in protection against SARS-CoV-2 infections and whether antibodies may play a role in promoting symptoms of COVID-19 remains unknown. In Project 1, we will define the heterogeneity of antibody responses produced during SARS-CoV-2 infections and test the hypothesis that particular antibody responses, with respect to the target antigen(s), specific epitopes and antibody effector functions, are required for protection against SARS-CoV-2 infections. We will perform studies under the following specific aims: Aim 1: Characterize antibodies elicited by SARS-CoV-2; Aim 2: Define antibody correlates of COVID-19 pathogenesis and protection. These studies will include structure determination by cryo-electron microscopy that will delineate the main binding epitopes and molecular characteristics of antibody recognition against the SARS-CoV-2 spike protein. Further, we will investigate whether there are antibody profiles that correlate with more severe outcomes in COVID-19. Results from these studies will guide the development of safe and effective vaccines and monoclonal antibodies for the prevention and treatment of COVID-19.

项目1：概要 通过数十年对感染性病原体的保护性免疫研究， 针对SARS-CoV-2的持久免疫需要抗体、B细胞和T细胞的特定功能特性 这需要通过详细的剧目研究来界定。人类对病毒感染的抗体反应是 多种多样，临床意义大相径庭。预先存在的反应性抗体或形成的抗体 在感染的早期，病毒颗粒可以参与，形成免疫复合物， 清除病毒。另一方面，免疫复合物也会促进炎症， 疾病的症状。SARS-CoV-2感染可以是无症状的，也可以引起疾病，COVID-19， 表现出一系列症状，从轻度到危及生命的肺炎和细胞因子 失调抗体在预防SARS-CoV-2感染中的作用以及抗体是否可以 在促进COVID-19症状方面发挥的作用仍然未知。在项目1中，我们将定义异质性 SARS-CoV-2感染过程中产生的抗体反应，并检验特定抗体 需要针对靶抗原、特异性表位和抗体效应子功能的应答 用于预防SARS-CoV-2感染。我们将根据以下具体目标进行研究：目标1： 表征SARS-CoV-2引发的抗体;目的2：确定COVID-19发病机制的抗体相关性 和保护.这些研究将包括通过冷冻电子显微镜进行结构测定， SARS-CoV-2刺突蛋白抗体识别的主要结合表位及分子特征 蛋白此外，我们将研究是否有抗体谱与更严重的结果相关 在COVID-19。这些研究的结果将指导开发安全有效的疫苗， 用于预防和治疗COVID-19的单克隆抗体。