System Biological Analyses of Adaptive Responses to vaccination

疫苗接种适应性反应的系统生物学分析

• 批准号: 10201503
• 负责人: Rafi Ahmed
• 金额: $ 230.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-13 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201503
• 关键词: 2019-nCoV; ATAC-seq; Address; Aspirate substance; Award; Blood; COVID-19; Cell Culture Techniques; Cells; Cloning; Competence; Diagnostic; Disease; Donor person; Epigenetic Process; Epithelial Cells; Epitopes; Genetic Transcription; Grant; Heterogeneity; Hospitals; Human; Immune; Immune response; Immune system; Immunity; Infection; Innate Immune Response; Knowledge; Learning; Lung; Lung Transplantation; Metabolic; Molecular; Molecular Profiling; Myelogenous; Myeloid Cells; Natural Immunity; Parents; Pathogenesis; Pathogenicity; Peripheral Blood Mononuclear Cell; Sampling; Science; Site; Stimulus; Structure of parenchyma of lung; Systems Biology; Therapeutic; Vaccination; Vaccine Design; Vaccines; Virus; Work; airway epithelium; biological systems; coronavirus disease; design; epigenomics; global health; imprint; indexing; insight; macrophage; metabolomics; monocyte; multiple omics; novel; pandemic disease; prevent; programs; response; single-cell RNA sequencing; transcriptome; transcriptomics; transplant centers

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) pandemic poses a major global health challenge. Coronavirus disease (COVID-19) is caused by SARSCoV-2 and represents the causative agent of a potentially fatal disease. Science has moved very rapidly in isolating, sequencing, and cloning the virus, and developing diagnostic kits, within a matter of weeks. However, major knowledge gaps remain about the dynamic interaction between the human immune system and the SARS-CoV-2. In particular, several fundamental questions regarding its pathogenesis, and the mechanisms of protective immunity that need to be induced by vaccination, remain unanswered. Learning how the immune system senses SARS-CoV-2 infection and orchestrates protective immunity is critical for designing effective vaccines and therapeutics. Our previous work using systems biology, multi-omics approaches to analyze immune responses to vaccination in humans has delineated molecular signatures of innate immunity to vaccination and infection and have provided rich mechanistic insights into the immune response1-7 . In this proposal, we propose a site-specific study to analyze samples from the IMPACC sub-study performed at Emory. We will use an integrated multi-omics approach (single cell transcriptomics, metabolomics, single cell epigenomics) to study innate immunity to COVID19 infection in humans. We will obtain PBMCs and tracheal aspirate samples from the IMPACC sub-study that will be conducted at Emory. We will address the following questions: What are the molecular and cellular signatures of the immune response to COVID-19 infection in the blood and tracheal aspirates of infected subjects? Does COVID-19 infection exert an epigenetic imprint of innate immunity? What is the molecular landscape and function of myeloid cell subsets and airway epithelial cells in the healthy lung, and following COVID-19 infection? These questions will be addressed in the following specific aims: 1) Determine the single cell transcriptional and epigenetic landscape of the immune response to COVID-19 infection in blood and tracheal aspirates, and 2) Determine the molecular identity and functions of myeloid cell subsets and epithelial cells in human lung and their response to COVID-19 infection. These studies will provide significant insight into the human immune response to COVID-19 infection that can be leveraged for designing vaccines and therapeutics to prevent or treat the infection.

小说的最新出现，致病性SARS-Coronavirus 2（SARS-COV-2）大流行 构成了全球重大的健康挑战。冠状病毒疾病（Covid-19）是由SARSCOV-2引起的，代表了潜在致命疾病的病因。科学的发展非常 快速隔离，测序和克隆病毒并在A内开发诊断试剂盒 数周的问题。但是，关于动态相互作用的主要知识差距仍然 人类免疫系统和SARS-COV-2。特别是几个基本问​​题 关于其发病机理以及需要诱导的保护性免疫的机制 通过疫苗接种，仍未得到答复。了解免疫系统如何感觉SARS-COV-2 感染和策划保护性免疫对于设计有效的疫苗和 疗法。我们以前使用系统生物学的工作，多词的方法来分析 对人类疫苗接种的免疫反应已划定了先天性的分子特征 对疫苗接种和感染的免疫力，并为免疫提供了丰富的机械见解 响应1-7 。在此提案中，我们提出了一项特定于地点的研究，以分析来自 Impacc子研究在Emory进行。我们将使用综合的多媒体方法（单一 细胞转录组学，代谢组学，单细胞表观基因组学）研究了对人类共同感染的先天免疫。我们将从IMPACC获得PBMC和气管抽吸样品 将在Emory进行的子研究。我们将解决以下问题：什么是 免疫反应的分子和细胞特征对血液和血液中的共同感染感染的反应 感染受试者的气管抽吸物？ COVID-19感染是否具有表观遗传印记 先天免疫？髓样细胞子集的分子景观和功能是什么 健康肺中的上皮细胞，以及在Covid-19感染之后？这些问题将是 在以下特定目的中解决：1）确定单细胞转录和 对血液和气管中共vid-19感染的免疫反应的表观遗传景观 抽吸物，2）确定髓样细胞亚群的分子身份和功能 人类肺中的上皮细胞及其对Covid-19感染的反应。这些研究将提供 对人类对COVID-19感染的免疫反应的重大见解，可以利用 用于设计疫苗和治疗剂以预防或治疗感染。