Longitudinal analysis to determine persistence of T cell responses induced by SARS-CoV-2 vaccination, natural infection with SARS-CoV-2, and human common cold coronaviruses

纵向分析以确定 SARS-CoV-2 疫苗接种、SARS-CoV-2 自然感染和人类普通感冒冠状病毒诱导的 T 细胞反应的持续性

• 批准号: 10619611
• 负责人: Alessandro Sette
• 金额: $ 65.65万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10619611
• 关键词: 2019-nCoV; Address; Age; Antigens; Authorization documentation; Blood specimen; CD8-Positive T-Lymphocytes; COVID-19 vaccination; COVID-19 vaccine; Cells; Clinical; Clone Cells; Common Cold; Communicable Diseases; Coronavirus; Cross-Sectional Studies; Cytomegalovirus; Data; Dose; Enrollment; Ethnic Origin; Evaluation; Exposure to; Human; Immune; Immunization; Individual; Infection; Influenza; Investigation; Longitudinal cohort; Measures; Molecular; Pathogenicity; Pattern; Persons; Pertussis; Phenotype; Property; RNA; Respiratory Tract Diseases; SARS-CoV-2 antigen; SARS-CoV-2 infection; Sampling; Sequence Analysis; Severity of illness; T cell clonality; T cell receptor repertoire sequencing; T cell response; T memory cell; T-Cell Receptor; T-Lymphocyte; Testing; Time; Vaccinated; Vaccination; Vaccinee; Vaccines; Virus; Yellow Fever; antigen-specific T cells; authority; biomarker panel; cohort; cross reactivity; longitudinal analysis; pathogen; pre-pandemic; recruit; respiratory pathogen; response; sex; single-cell RNA sequencing; transcriptome; transcriptomics; unvaccinated; vaccination outcome; vaccine platform; vaccine trial

Project Summary: Project 1 The current LJI HIPC Proposal focuses on common pathogens causing infectious diseases of the respiratory tract. Here in Project 1, our focus is to define changes of antigen-specific T cell responses to SARS-CoV-2 vaccination over time, up to 3 years post vaccination; and compare them to those observed in natural infection or previously-infected, but now recently-vaccinated subjects. We will examine T cell phenotypes defined by cytometric analysis of reference panels of markers. T cell sub- populations defined by transcriptomes of single-cells, and T cell clonality defined by single-cell T cell receptor (TCR) sequence analysis. These unbiased studies will define features associated with the magnitude and persistence of antigen-specific T cell responses. The data generated in the context of SARS-CoV-2 will then be compared the data to T cell responses induced by natural infection with common cold coronaviruses (CCC). This will provide a comparator with other much less pathogenic coronaviruses. Our studies will further detail and compare the results of vaccination with different SARS-CoV-2 vaccine platforms (Moderna, Pfizer, J&J and others that might be authorized). In parallel, we will investigate samples from two studies involving two commonly utilized vaccines, namely those against Yellow Fever and Pertussis. Finally, our studies will also provide a large cross-sectional cohort, to address, on one hand, differences in disease severity, ranging from mild to moderate to severe, and the impact of variables such as age, sex, ethnicity, disease severity, and exposure to CCC viruses on the magnitude and persistence of vaccine-induced T cell responses.

项目概要：项目1 LJI重债穷国倡议目前的提案侧重于引起呼吸道传染病的常见病原体， 道。在项目1中，我们的重点是确定抗原特异性T细胞对SARS-CoV-2应答的变化 随着时间的推移，接种疫苗后最多3年;并将其与自然感染中观察到的结果进行比较 或者之前感染过但最近接种过疫苗的人 我们将检查T细胞表型定义的细胞计数分析参考面板的标志物。T细胞亚群 由单细胞转录组定义的群体，以及由单细胞T细胞受体定义的T细胞克隆性 (TCR)序列分析这些无偏见的研究将定义与震级相关的特征， 抗原特异性T细胞应答的持久性。 然后将SARS-CoV-2背景下产生的数据与诱导的T细胞应答进行比较。 普通感冒冠状病毒（CCC）的自然感染。这将提供一个比较器与其他少得多 致病性冠状病毒。 我们的研究将进一步详细说明和比较不同SARS-CoV-2疫苗的接种结果 平台（Moderna、辉瑞、强生和其他可能获得授权的公司）。同时，我们将调查样本 两项研究涉及两种常用疫苗，即黄热病和百日咳疫苗。 最后，我们的研究还将提供一个大型的横断面队列，一方面， 疾病严重程度，从轻度到中度到重度，以及年龄，性别，种族， 疾病严重程度和暴露于CCC病毒对疫苗诱导的T细胞免疫应答的强度和持续性的影响 应答