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Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2 (JH-EPICS)

约翰·霍普金斯大学 SARS-CoV-2 发病机制和免疫卓越中心 (JH-EPICS)

基本信息

批准号：
10706725
负责人：
ANDREA L COX
金额：
$ 11.97万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706725
关键词：
2019-nCoV Address Affect Age Antibodies Antibody Response Antibody-mediated protection Antigens Basic Science Biometry COVID-19 COVID-19 patient COVID-19 severity Cell surface Cells Cessation of life Clinical Clinical Sciences Collaborations Communicable Diseases Complement Complex Coupled Data Analyses Development Diabetes Mellitus Disease Ensure Enzyme-Linked Immunosorbent Assay Epidemiologic Monitoring Epidemiology Ethnic Origin Evaluation Flow Cytometry Foundations Gender Goals HIV Health Healthcare Systems Heart Diseases Human Immune Immune response Immunity Immunoglobulin Class Switching Immunology Immunomodulators Infant Infection Inflammasome Inflammatory Response Infrastructure Interdisciplinary Study International Leadership Mediating Metabolic Methods Mission Modeling Monoclonal Antibody Therapy Myeloid-derived suppressor cells Outcome Pathogenesis Pathologic Pathology Patients Peripheral Blood Mononuclear Cell Persons Population Prospective cohort Proteins Protocols documentation Public Health Race Reagent Regimen Reporting Research Research Activity Research Personnel Research Project Grants Resources Respiratory Tract Infections Risk SARS-CoV-2 antibody SARS-CoV-2 immune response SARS-CoV-2 immunity SARS-CoV-2 infection Sampling Science Serology Serology test Severity of illness Sex Differences Solid Stains Statistical Data Interpretation Statistical Models Surrogate Markers Symptoms T-Lymphocyte Testing Therapeutic Training Translational Research Ursidae Family Vaccine Design Viral Viral Pathogenesis Virus age difference antibody-dependent cell cytotoxicity base biosafety level 3 facility comorbidity experimental study gender difference innate immune sensing insight intersectionality male neutralizing antibody new therapeutic target novel novel marker organ transplant recipient pandemic disease racial difference rational design response sample fixation severe COVID-19 sex single cell analysis therapeutic evaluation therapy development vaccine candidate vaccine development vaccine evaluation virology

项目摘要

Johns Hopkins has broad expertise in the science of human health, with viral immunity, pathogenesis, epidemiology, biostatistics, and surveillance emerging as integral components of the multidisciplinary research mounted at Johns Hopkins during the current pandemic. We have operated a Serological Sciences Center of Excellence: the Johns Hopkins Excellence in Pathogenesis and Immunity Center for SARS-CoV-2 (JH-EPICS). The overarching goal of JH-EPICS since 2020 with ongoing projects to distinguish immune responses that protect from those that cause pathology during infection and to analyze vaccine induced immune responses. We have resources and samples available to systematically evaluate innate, T cell, and antibody responses to SARS-CoV-2 in peripheral blood mononuclear cells and serological samples from COVID-19 vaccine recipients and patients sampled longitudinally. JH-EPICS contains three interconnecting Research Projects (RPs). RP1 focuses on innate immune sensing and activation of the human inflammasome by SARS-CoV-2, with evaluation of how anti-SARS-CoV-2 antibodies modulate innate sensing. RP2 uses traditional techniques to assess T cell responses, including ELISpot, and a novel flow-cytometry based platform that enables single cell analysis of cell surface markers combined with intracellular staining for proteins involved in metabolic programming. In RP3, the magnitude, duration, and class switching of SARS-CoV-2-specific antibody isotypes as well as virus-specific neutralizing antibody responses is analyzed and compared with non-neutralizing antibody functions, e.g., complement fixation and antibody-dependent cellular cytotoxicity, using a novel core set of serological assays. A centralized Virology Reagent Core provides antigen for ELISAs, reagents to identify virus-specific immune cell populations, inactivated SARS-CoV-2 viruses, methods for quantifying SARS-CoV-2, and access to biosafety level 3 facilities and training needed to perform any experiments involving live SARS-CoV-2. The Analysis Resource Core provides statistical modeling and analysis to frame and test hypotheses about the mechanisms mediating the severity of COVID-19 as well as the intersectionality of sex, gender, age, and racial differences in immune mechanisms of COVID-19 disease and vaccination. In concert with the trans-network collaborations, this research provides significant insights into pathologic immune responses to SARS-CoV-2 and elucidates mechanisms of immunity against SARS-CoV-2 infection and vaccination. By uncovering the correlates of protective immunity following boosting, JH-EPICS research will further enhance vaccine design and evaluation of vaccine candidates.

约翰·霍普金斯大学在人类健康科学方面拥有广泛的专业知识，病毒免疫、发病机制、流行病学、生物统计学和监测已成为约翰·霍普金斯大学在当前大流行期间开展的多学科研究的组成部分。我们运营着一个血清学科学卓越中心：约翰霍普金斯大学 SARS-CoV-2 发病机制和免疫卓越中心 (JH-EPICS)。自 2020 年以来，JH-EPICS 的总体目标是区分免疫反应，以防止感染过程中引起病理的免疫反应，并分析疫苗诱导的免疫反应。我们拥有可用的资源和样本，可系统评估外周血单核细胞以及纵向采样的 COVID-19 疫苗接种者和患者的血清学样本中对 SARS-CoV-2 的先天反应、T 细胞和抗体反应。 JH-EPICS 包含三个相互关联的研究项目 (RP)。 RP1 专注于先天免疫感应和 SARS-CoV-2 对人类炎症体的激活，并评估抗 SARS-CoV-2 抗体如何调节先天感应。 RP2 使用传统技术评估 T 细胞反应，包括 ELISpot 和基于新型流式细胞术的平台，该平台能够对细胞表面标记物进行单细胞分析，并结合对参与代谢编程的蛋白质进行细胞内染色。在 RP3 中，使用一套新颖的核心血清学检测方法，分析了 SARS-CoV-2 特异性抗体同种型以及病毒特异性中和抗体反应的幅度、持续时间和类别转换，并与非中和抗体功能（例如补体结合和抗体依赖性细胞毒性）进行比较。集中式病毒学试剂核心提供 ELISA 抗原、识别病毒特异性免疫细胞群的试剂、灭活的 SARS-CoV-2 病毒、量化 SARS-CoV-2 的方法，以及进行涉及活 SARS-CoV-2 的任何实验所需的生物安全 3 级设施和培训。分析资源核心提供统计建模和分析，以构建和测试有关调节 COVID-19 严重程度的机制的假设，以及性别、性别、年龄和种族差异在 COVID-19 疾病和疫苗接种免疫机制中的交叉性。与跨网络合作相结合，这项研究提供了对 SARS-CoV-2 病理免疫反应的重要见解，并阐明了针对 SARS-CoV-2 感染和疫苗接种的免疫机制。通过揭示加强免疫后保护性免疫的相关性，JH-EPICS 研究将进一步加强疫苗设计和候选疫苗的评估。