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)

• 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
• 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

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、生物统计学和监测是当前大流行期间约翰霍普金斯大学开展的多学科研究的组成部分。我们运营了一个血清学科学卓越中心：约翰霍普金斯SARS-CoV-2发病机制和免疫卓越中心（JH-EPICS）。自2020年以来，JH-EPICS的总体目标是通过正在进行的项目来区分免疫反应，这些免疫反应可以保护感染期间引起病理学的免疫反应，并分析疫苗诱导的免疫反应。我们有资源和样本可用于系统地评估外周血单核细胞和血清学样本中SARS-CoV-2的先天性、T细胞和抗体反应，这些样本来自COVID-19疫苗接种者和纵向采样的患者。JH-EPICS包含三个相互关联的研究项目（RP）。RP 1主要研究SARS-CoV-2对人类炎性小体的先天免疫感知和激活，并评估抗SARS-CoV-2抗体如何调节先天免疫感知。RP 2使用传统技术来评估T细胞反应，包括ELISpot和一种新型的基于流式细胞术的平台，该平台能够对细胞表面标志物进行单细胞分析，并结合细胞内染色来检测参与代谢编程的蛋白质。在RP 3中，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应答的幅度、持续时间和类别转换，并与非中和抗体功能进行比较，例如，补体结合和抗体依赖性细胞毒性，使用一套新的核心血清学试验。一个集中的病毒学试剂核心提供ELISA的抗原，用于识别病毒特异性免疫细胞群的试剂，灭活的SARS-CoV-2病毒，定量SARS-CoV-2的方法，以及进行任何涉及活SARS-CoV-2的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，以构建和检验有关COVID-19严重程度介导机制的假设，以及COVID-19疾病和疫苗接种免疫机制中性别、性别、年龄和种族差异的交叉性。与跨网络合作一致，这项研究为SARS-CoV-2的病理免疫反应提供了重要的见解，并阐明了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。