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

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、生物统计学和监测正在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。我们运营了一个卓越的血清学科学中心：约翰霍普金斯大学卓越的SARS-CoV-2发病机制和免疫中心（JH-EPICS）。自2020年以来，JH-EPICS的总体目标是正在进行的项目，以区分在感染期间引起病理的免疫反应，并分析疫苗诱导的免疫反应。我们有资源和样本可以系统地评估COVID-19疫苗接种者和患者外周血单个核细胞和血清学样本中对SARS-CoV-2的先天、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关注的是SARS-CoV-2对人炎性小体的先天免疫感知和激活，并评估抗SARS-CoV-2抗体如何调节先天感知。RP2使用传统技术来评估T细胞反应，包括ELISpot和一种新的基于流式细胞术的平台，该平台能够对细胞表面标记物进行单细胞分析，并结合细胞内染色来检测参与代谢编程的蛋白质。在RP3中，使用一套新的核心血清学分析方法，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、持续时间和类别转换，并将其与非中和抗体功能（如补体固定和抗体依赖的细胞毒性）进行了比较。集中的病毒学试剂核心为elisa提供抗原、鉴定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，以及获得进行任何涉及活体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，以构建和检验关于介导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疾病和疫苗接种的免疫机制中的交叉性。与跨网络合作一致，本研究为SARS-CoV-2的病理免疫反应提供了重要见解，并阐明了针对SARS-CoV-2感染和疫苗接种的免疫机制。通过揭示增强后保护性免疫的相关因素，JH-EPICS研究将进一步加强疫苗设计和候选疫苗的评估。

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.