Cellular Immunity and Memory to SARS-CoV-2

细胞对 SARS-CoV-2 的免疫和记忆

• 批准号: 10222404
• 负责人: Elizabeth B Norton
• 金额: $ 94.01万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222404
• 关键词: 2019-nCoV; Adult; Antibodies; Antigens; Antiviral Agents; Area; B-Lymphocytes; Biological Assay; Black race; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; Cells; Cellular Immunity; Child; Childhood; Clinical; Communities; Complement; Coronavirus; DNA; Disease; Environmental Risk Factor; Enzyme-Linked Immunosorbent Assay; Ethnic Origin; Evaluation; Feces; Goals; Haplotypes; Hispanics; Home environment; Household; Immune response; Immunity; Immunoassay; Immunoglobulin G; Immunoglobulin-Secreting Cells; Immunologic Memory; Immunologic Tests; Income; Individual; Infection; Influenza; Integration Host Factors; Length; Longevity; Louisiana; Malignant Neoplasms; Measures; Memory; Memory B-Lymphocyte; Minority; Modeling; Mucosal Immunity; Mucous Membrane; Mus; Peptides; Poliomyelitis; Population; Proteins; Public Health; Relaxation; Respiratory System; Saliva; Sampling; Serological; Seroprevalences; Serum; Shapes; Statistical Data Interpretation; T cell response; T-Cell Activation; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Tetanus Toxoid; Time; Universities; Vaccination; Vaccines; Viral; Virus; Virus Diseases; cancer diagnosis; cohort; coronavirus disease; cytokine; human subject; member; pandemic disease; pathogen; peripheral blood; residence; response; retinal S antigen peptide M; telomere

Project 2 Summary The goal of Project 2 is to better characterize the cellular immunity and memory to SARS-CoV-2. This project will complement Project 1 by defining correlates of cellular immunity, including CD4 T-cell, CD8 T-cell, and B- cell memory, which may be longer lasting than serological responses. Like Project 1, Project 2 will use samples collected from the Clinical Cohort Core and many of the assays developed by the ImmunoAssay Core. Uniquely, because our clinical cohorts include pediatric and adult subjects, large numbers of minorities (35-50%), and a cancer cohort, we will be able to test for immune response differences in a number of distinct populations. During the proposal period, we will complete the following aims: (1) Define the cellular responses established after SARS-CoV-2 infection and differences between human subject cohorts. CD4+ and CD8+ T- cell activation will be determined after stimulation with SARS-CoV-2 S, N and M peptides and compared to antibody-secreting cells. We will also examine if any of these responses are recapitulated in mouse COVID-19 models. (2) Identify responses to individual T-cell epitopes of SARS-CoV-2 and whether MHC-II haplotypes are associated with ‘unstable’ T-cell epitopes, and thus weak B-cell responses. (3) Identify persistence of SARS- CoV-2 memory responses and differences between human subject cohorts. This includes changes to cellular and serological immunity over time. By assaying mucosal responses in the respiratory tract, as well as saliva and feces, we will also evaluate mucosal immunity versus peripheral blood responses. (4) Define the relationship between SARS-CoV-2 exposure and immunologic memory to other pathogens. We will compare the serological response to other viruses including seasonal coronaviruses, influenza, polio and MMR as well as tetanus toxoid in samples collected before the current pandemic and after its onset. Identifying if SARS- CoV-2 infection alters immunity to other pathogens or vaccines. All studies will be performed using samples from cohorts across the lifespan and among those with and without a cancer diagnosis. At the completion of the proposal period, the aims described above will result in a major advance in our understanding of T-cell and B-cell memory to SARS-CoV-2 and relationship to serological evaluation in Project 1. Such advancements are critical to our understanding of the serological response to SARS-CoV-2 as well as the ultimate understanding of protective immunity to viral infection or even vaccination.

项目二总结