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

项目摘要：项目1 目前的LJI重债穷国倡议侧重于引起呼吸道传染病的常见病原体。 一条小路。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的反应的变化 随着时间的推移接种疫苗，接种后长达3年；并将它们与在自然感染中观察到的情况进行比较 或以前感染过，但最近接种过疫苗的受试者。 我们将通过标记物的细胞学分析来检测T细胞表型。T细胞亚群 由单细胞转录本定义的群体和由单细胞T细胞受体定义的T细胞克隆性 (TCR)序列分析。这些不偏不倚的研究将定义与震级和 抗原特异性T细胞反应的持久性。 然后，在SARS-CoV-2背景下产生的数据将与诱导的T细胞反应进行比较 通过自然感染普通感冒冠状病毒(CCC)。这将提供一个具有其他少得多的比较器 致病冠状病毒。 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(莫德纳、辉瑞、强生和其他可能获得授权的公司)。同时，我们将对样本进行调查 来自两项涉及两种常用疫苗的研究，即针对黄热病和百日咳的疫苗。 最后，我们的研究还将提供一个大的横断面队列，以一方面解决在 疾病严重程度，从轻度到中度再到重度，以及年龄、性别、种族、 疾病严重程度和接触CCC病毒对疫苗诱导的T细胞数量和持久性的影响 回应。

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.