Cellular Immunity and Memory to SARS-CoV-2

细胞对 SARS-CoV-2 的免疫和记忆

• 批准号: 10688393
• 负责人: Elizabeth B Norton
• 金额: $ 39.65万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10688393
• 关键词: 2019-nCoV; Adult; Antibodies; Antibody-mediated protection; Antigens; 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; DNA; Disease; Environmental Risk Factor; Enzyme-Linked Immunosorbent Assay; Ethnic Origin; Evaluation; Feces; Goals; Haplotypes; Hispanic; Home; 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; SARS-CoV-2 exposure; SARS-CoV-2 immunity; SARS-CoV-2 infection; Saliva; Sampling; Serology; 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; post SARS-CoV-2 infection; residence; response; retinal S antigen peptide M; seasonal coronavirus; 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总结 项目 2 的目标是更好地表征 SARS-CoV-2 的细胞免疫和记忆。 将通过定义细胞免疫的相关性来补充项目 1，包括 CD4 T 细胞、CD8 T 细胞和 B- 与项目 1 一样，项目 2 将使用细胞记忆。 从临床队列核心和免疫测定开发的许多测定中收集的样本 核心在于，我们的临床队列包括儿童和成人受试者以及大量少数族裔。 （35-50%）和癌症队列，我们​​将能够测试许多不同的免疫反应差异 在提案期间，我们将完成以下目标：（1）定义细胞反应。 SARS-CoV-2 感染后建立的以及人类受试者群体 CD4+ 和 CD8+ T- 之间的差异。 用 SARS-CoV-2 S、N 和 M 肽刺激后，将确定细胞活化情况，并与 我们还将检查小鼠 COVID-19 中是否重现了这些反应。 (2) 确定对 SARS-CoV-2 单个 T 细胞表位的反应以及 MHC-II 单倍型是否是 与“不稳定”T 细胞表位相关，因此 B 细胞反应较弱 (3) 识别 SARS- 的持续性。 CoV-2 记忆反应和人类受试者群体之间的差异这包括细胞的变化。 随着时间的推移，通过检测呼吸道粘膜反应以及唾液来检测血清学免疫。 (4) 定义 我们将比较 SARS-CoV-2 暴露与对其他病原体的免疫记忆之间的关系。 对其他病毒的血清学反应，包括季节性冠状病毒、流感、脊髓灰质炎和 MMR 在当前大流行之前和爆发之后收集的样本中鉴定出破伤风类毒素。 CoV-2 感染会改变对其他病原体或疫苗的免疫力。所有研究都将使用样本进行。 来自整个生命周期的队列以及完成癌症诊断的人群。 在提案期间，上述目标将导致我们对 T 细胞和 项目 1 中 B 细胞对 SARS-CoV-2 的记忆以及与血清学评估的关系。这些进展是 对于我们理解 SARS-CoV-2 的血清学反应以及最终理解至关重要 对病毒感染甚至疫苗接种的保护性免疫力。