Project 1: Serology

项目1：血清学

• 批准号: 10688364
• 负责人: Taia Wang
• 金额: $ 43.93万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10688364
• 关键词: 2019-nCoV; Alanine; Amino Acids; Antibodies; Antibody Response; Antibody Specificity; Antigen Targeting; Antigen-Antibody Complex; B-Lymphocytes; Binding; COVID-19; COVID-19 pandemic; COVID-19 pathogenesis; COVID-19 patient; COVID-19 treatment; COVID-19 vaccine; 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; Patients; Persons; Phenotype; Play; Pneumonia; Population; Prevention; Property; Proteins; RNA Viruses; Research; Research Personnel; Resolution; Role; SARS-CoV-2 immunity; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Sampling; Sampling Studies; Serology; Sorting - Cell Movement; Specificity; Structure; Symptoms; T-Lymphocyte; Testing; Therapeutic Monoclonal Antibodies; Therapeutic antibodies; Vaccine Adjuvant; Vaccine Design; Viral Antigens; Viral Proteins; Virion; Virus; Virus Diseases; Work; clinically significant; cytokine; design; mutant; novel vaccines; passive antibodies; pathogen; reconstitution; response; seropositive; severe COVID-19; tool; trend; vaccine development; vaccine efficacy; vaccine-induced antibodies

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.

项目一：总结