Admin-Core-001

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，包括病毒免疫、发病机制、 流行病学、生物统计学和监测正在成为多学科研究的组成部分 在目前的大流行期间，在约翰霍普金斯大学安装了。我们建议发展一门血清学科学 卓越中心：约翰霍普金斯大学SARS-CoV-2致病和免疫卓越中心 (JH-EPICS)。JH-EPICS的首要目标是区分保护和 在感染过程中会导致病理改变。在克莱恩博士和考克斯博士的多重PI领导下，JH-EPICS 管理核心将确保资源和样本可用来系统地评估先天T细胞， 和对SARS-CoV-2的抗体反应在外周血单核细胞和血清样本中 新冠肺炎患者进行了纵向采样。JH-EPICS包含三个相互关联的研究项目(RPS)。 RP1专注于SARS-CoV-2对人类炎症体的先天免疫感知和激活， 评价抗SARS-CoV-2抗体如何调节先天感觉。RP2使用一种新的流式细胞术 基于平台，支持将传统细胞表面标记与细胞内标记相结合的单细胞分析 对参与代谢编程的蛋白质进行染色。使用这个平台，我们已经识别出不同的髓系 新冠肺炎中含有丰富的衍生抑制细胞(MDSCs)和T细胞。RP1将描述这些MDSC的特征， 而RP2将探索在新冠肺炎患者中发现的T细胞的新群体。RP2也将定义小说 生物标志物，以预测疾病的严重程度，跟踪疾病的进程，并定义新的替代物 测试治疗方案的标记物。RP1和RP2将共同确定新的治疗靶点。在……里面 RP3、SARS-CoV-2特异性抗体亚型的大小、持续时间和类别转换以及病毒- 将分析特异性中和抗体反应，并与非中和抗体进行比较。 功能，例如，补体结合和抗体依赖的细胞毒性，使用一套新的核心 血清学检测。一个集中的病毒学试剂核心将为ELISA提供抗原，用于鉴定试剂 病毒特异性免疫细胞群，灭活的SARS-CoV-2病毒，定量SARS-CoV的方法 2，以及获得生物安全3级设施和进行涉及现场的任何实验所需的培训 SARS-CoV-2。分析资源核心将为框架和测试提供统计建模和分析 关于调节新冠肺炎严重程度以及性交叉性的机制的假说， 新冠肺炎免疫机制的性别、年龄和种族差异。与跨国网络协同工作 合作，这项研究将为SARS-CoV-2的病理免疫反应提供重要的见解， 新的治疗靶点的确定和对SARS-CoV-2感染免疫的定义。通过 发现保护性免疫的相关性，JH-EPICS研究将进一步加强疫苗设计和 对候选疫苗的评估。

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 propose development of 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 is to distinguish immune responses that protect from those that cause pathology during infection. Under the Multiple PI leadership of Drs. Klein and Cox, the JH-EPICS Administrative Core will ensure resources and samples are 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 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 a novel flow-cytometry based platform that enables single cell analysis of traditional cell surface markers combined with intracellular staining for proteins involved in metabolic programming. Using this platform, we have identified distinct myeloid derived suppressor cells (MDSCs) and T cells abundant in COVID-19. RP1 will characterize these MDSCs, while RP2 will explore novel populations of T cells identified in COVID-19 patients. RP2 will also define novel biomarkers in order to predict severity of disease, track the course of disease, and define novel surrogate markers for testing therapeutic regimens. Together, RP1 and RP2 will identify novel therapeutic targets. In RP3, the magnitude, duration, and class switching of SARS-CoV-2-specific antibody isotypes as well as virus- specific neutralizing antibody responses will be 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 will provide 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 will provide 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. In concert with the trans-network collaborations, this research will provide significant insights into pathologic immune responses to SARS-CoV-2, identification of novel therapeutic targets, and definition of immunity against SARS-CoV-2 infection. By uncovering the correlates of protective immunity, JH-EPICS research will further enhance vaccine design and evaluation of vaccine candidates.