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（Johns Hopkins）在人类健康科学方面拥有广泛的专业知识，具有病毒免疫，发病机理，流行病学，生物统计学和监测，作为当前大流行期间约翰·霍普金斯（Johns Hopkins）的多学科研究的组成部分。我们经营着一个卓越的血清学科学中心：约翰·霍普金斯（Johns Hopkins）在SARS-COV-2（JH-EPICS）的发病机理和免疫中心卓越。自2020年以来，JH-EPIC的总体目标是持续的项目，以区分保护免受感染过程中引起病理和分析疫苗诱导免疫反应的免疫反应的免疫反应。我们有资源和样品可用于系统地评估外周血单核细胞中对SARS-COV-2的先天，T细胞和抗体反应，以及来自COVID-19-19S疫苗接受者的血清学样本和纵向取样的患者。 JH-EPIC包含三个互连研究项目（RPS）。 RP1专注于SARS-COV-2对人类炎症体的先天免疫传感和激活，并评估抗SARS-COV-2抗体如何调节先天感应。 RP2使用传统技术来评估包括ELISPOT在内的T细胞反应，以及一个新型的基于流动性的平台，该平台能够对细胞表面标记的单细胞分析与参与代谢编程的蛋白质结合使用细胞内染色。在RP3中，分析了SARS-COV-2特异性抗体同型以及病毒特异性中和抗体反应的大小，持续时间和类切换，并与非中和抗体功能（例如，使用新颖的综合核心核心组合的补体固定和抗体依赖的细胞毒性核心）进行了比较。一种集中的病毒学试剂核心为ELISA提供抗原，试剂，以鉴定病毒特异性免疫细胞群体，灭活的SARS-COV-2病毒，量化SARS-COV-2的方法以及对执行涉及活SARS-COV-2的任何实验所需的生物安全3级设施和训练所需的培训。分析资源核心提供了统计建模和分析，以构建和检验有关介导COVID-19的严重程度以及性别，性别，年龄和种族差异的机制的机制的假设。在与跨网络协作的一致过程中，这项研究为对SARS-COV-2的病理免疫反应提供了重要的见解，并阐明了针对SARS-COV-2感染和疫苗接种的免疫力机制。通过揭示促进后保护性免疫的相关性，JH-EPICS研究将进一步增强疫苗候选疫苗的设计和评估。