Antigen specific T cell responses to two different strains of SARS-CoV-2

项目总结 冠状病毒病2019年(新冠肺炎)是由SARS-CoV-2引起的一种新兴传染病 病毒。在过去的4个月里，这种疾病已经导致超过120万美国人患病。然而， 几乎没有关于人类对这种病毒的细胞免疫反应的数据。监测动力学和 与新冠肺炎临床缓解相关的细胞免疫反应的广度应该有助于了解 人类在自然感染期间对这种病原体的免疫反应。我们将评估SARS-CoV-2抗原 不同疾病严重程度的受试者感染 美国-WAS2/2020类毒株或FR-HF1465/2020类毒株，这是华盛顿流行的两种主要毒株 州政府。我们将检验这一假设，即协调的CD4+和CD8+抗原特异性反应是 用来清除病毒。我们还将测试这一假设，即患有严重疾病的受试者和那些 死于该病的人有功能失调的CD4+T细胞反应。我们将使用转录分析来 评估全血、大量T细胞和抗原特异性的CD4+和CD8+T细胞。数据将按以下方式分层 病毒的种类和疾病的严重性。主要有三个目标：1.抗原特异性免疫的特征 新冠肺炎重症肺炎、中度肺炎和轻症肺炎患者的免疫反应 美国-WAS2/2020毒株或FR-HF1465/2020毒株。2.表位特异性免疫反应的特征 在新冠肺炎的受试者中。受试者抗原特异性CD4+T细胞功能缺陷的假说 患有严重疾病的人将接受测试。3.新冠肺炎呼吸道感染宿主核糖核酸序列特征分析 在新冠肺炎感染者的全血PBMC中，大量和病毒抗原特异性的CD_4~+和CD_8~+T细胞 由美国-WAS2/2020菌株或类似FR-HF1465/2020菌株。更好地了解抗原 人类的特异性免疫反应应有助于确定有效的候选治疗药物 以及开发预防感染的新疫苗。

PROJECT SUMMARY Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that is caused by the SARS-CoV-2 virus. The disease has caused illness in more than 1.2 million Americans within the last 4 months. However, there are almost no data on human cellular immune response towards this virus. Monitoring the kinetics and breadth of cellular immune responses associated with clinical resolution of COVID-19 should shed insight on the human immune response towards this pathogen during natural infection. We will evaluate SARS-CoV-2 antigen specific immune responses in subjects with different degree of disease severity that are infected by either the USA-WAS2/2020 like strain or the FR-HF1465/2020 like strain, the 2 major strains that circulated in Washington state. We will test the hypothesis that coordinated CD4+ and CD8+ antigen specific responses are responsible for clearing of the virus. We will also test the hypothesis that subjects that have severe disease and those that succumb to the disease have dysfunctional CD4+T cell responses. We will use transcriptomics analysis to evaluate whole blood, bulk T cells and antigen specific CD4+ and CD8+ T cells. Data will be stratified according to the viral strains and disease severity. There will be 3 major aims: 1. Characterize of antigen specific immune responses in COVID-19 subjects with severe pneumonia, moderate disease and mild disease, infected by either the USA-WAS2/2020 strain or the FR-HF1465/2020 strain. 2. Characterize epitope specific immune response in subjects with COVID-19. The hypothesis that the functional defect of antigen specific CD4+ T cells in subjects with severe disease will be tested. 3. Characterize host RNA-seq signatures of COVID-19 respiratory infection in whole blood PBMC, bulk and viral antigen-specific CD4+ and CD8+ T cells from COVID-19 subjects infected by either the USA-WAS2/2020 strain or the FR-HF1465/2020 like strain. A better understanding of antigen specific immune responses in human should facilitate the identification of effective drug candidates for treatment and developing new vaccine to prevent infection.