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

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.