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2摘要 项目2的目标是更好地表征SARS-COV-2的蜂窝免疫和记忆 将通过定义细胞免疫，含CD4 T细胞，CD8 T细胞和B-的相关性来补充项目1 细胞内存可能比serolololocal响应更长。 从临床队列核心收集的样品以及免疫测定法进行的许多测定 核心。 （35-50％）和癌症队列，我们​​将能够测试许多不同的不同的反应差异 人群。在提案期间，我们将完成以下目的：（1） 在SARS-COV-2感染和人类受试者队列之间的差异之后建立。 用SARS-COV-2 S，N和M肽刺激后，将确定细胞激活，并进行比较 抗体分泌细胞。 模型（2）确定对SARS-COV-2的单个T细胞表位的反应 与“不稳定”的T细胞表位相关，因此B细胞响应弱。 COV-2记忆响应和差异subeen人类主体人群。 随着时间的流逝，血清学免疫。 和粪便，我们还将评估粘膜免疫与外周血反应（4） SARS-COV-2暴露与其他病原体的免疫记忆之间的关系 还对其他病毒的血清学反应也包括季节性冠状病毒，流感，小儿麻痹症和MMR 确定在当前大流行之前和发作之前收集的样品中的SARS-，作为破伤风毒素。 COV-2感染改变了其他针对其他研究的疫苗。 从整个生命周期中以及没有癌症诊断的人群中。 提案期间，所描述的目的将导致我们对T细胞的理解和 B细胞记忆到SARS-COV-2以及项目1中与血清学评估的关系。此类进步是 对了解SARS-COV-2的血清学反应以及理解至关重要 对病毒感染甚至疫苗接种的保护性免疫。