Core-001

核心001

• 批准号: 10187732
• 负责人: William W. Kwok
• 金额: $ 33.27万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187732
• 关键词: 2019-nCoV; Affect; American; Antigens; CD3 Antigens; CD4 Positive T Lymphocytes; CD8 Antigens; CD8-Positive T-Lymphocytes; CD8B1 gene; COVID-19; Cessation of life; Clinical; Coronavirus; Data; Defect; Disease; Emerging Communicable Diseases; Epitopes; Eragrostis; Health; Human; Immune response; Infection; Infection prevention; Institutes; Kinetics; Link; Lymphoid Cell; Monitor; Outcome; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Pneumonia; Regulatory T-Lymphocyte; Resolution; Respiratory Tract Infections; Severe Acute Respiratory Syndrome; Severity of illness; Structural Protein; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Transcript; Viral; Viral Antigens; Virus; Washington; Whole Blood; antigen-specific T cells; cross reactivity; drug candidate; insight; novel vaccines; pathogen; response; therapeutic development; transcriptome sequencing; transcriptomics; vaccine development

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.

项目摘要 冠状病毒疾病2019（COVID-19）是一种新兴的传染病，是由SARS-COV-2引起的 病毒。在过去的四个月内，这种疾病已导致超过120万美国人的疾病。然而， 几乎没有关于人类细胞免疫反应对该病毒的数据。监测动力学和 与COVID-19的临床分辨率相关的细胞免疫反应的广度应洞悉 人类对自然感染期间这种病原体的免疫反应。我们将评估SARS-COV-2抗原 在不同程度的疾病严重程度的受试者中，特定的免疫反应感染了 USA-WAS2/2020，例如应变或FR-HF1465/2020，例如应变，这是华盛顿循环的2个主要菌株 状态。我们将检验以下假设：协调的CD4+和CD8+抗原特定反应是负责的 用于清除病毒。我们还将检验以下假设，即患有严重疾病的受试者 屈服于该疾病的CD4+T细胞反应功能失调。我们将使用转录组学分析来 评估全血，大量T细胞和抗原特异性CD4+和CD8+ T细胞。数据将根据 病毒株和疾病的严重程度。将有3个主要目标：1。特异性免疫的特征 COVID-19患有严重肺炎，中度疾病和轻度疾病的受试者的反应，由任何一种感染 USA-WAS2/2020应变或FR-HF1465/2020菌株。 2。表征表位特异性免疫反应 在Covid-19的受试者中。受试者中抗原特异性CD4+ T细胞的功能缺陷的假设 将测试严重疾病。 3。表征COVID-19的宿主RNA-seq签名 在全血PBMC中，来自COVID-19受试者感染的散装和病毒抗原特异性CD4+和CD8+ T细胞 通过USA-WAS2/2020菌株或FR-HF1465/2020的菌株。更好地了解抗原 人类的特定免疫反应应促进鉴定有效的治疗药物 并开发新的疫苗以防止感染。