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 researchmounted at Johns Hopkins during the current pandemic. We propose development of a Serological SciencesCenter 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 thosethat cause pathology during infection. Under the Multiple PI leadership of Drs. Klein and Cox, the JH-EPICSAdministrative 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 fromCOVID-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, withevaluation of how anti-SARS-CoV-2 antibodies modulate innate sensing. RP2 uses a novel flow-cytometrybased platform that enables single cell analysis of traditional cell surface markers combined with intracellularstaining for proteins involved in metabolic programming. Using this platform, we have identified distinct myeloidderived 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 novelbiomarkers in order to predict severity of disease, track the course of disease, and define novel surrogatemarkers for testing therapeutic regimens. Together, RP1 and RP2 will identify novel therapeutic targets. InRP3, 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 antibodyfunctions, e.g., complement fixation and antibody-dependent cellular cytotoxicity, using a novel core set ofserological assays. A centralized Virology Reagent Core will provide antigen for ELISAs, reagents to identifyvirus-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 liveSARS-CoV-2. The Analysis Resource Core will provide statistical modeling and analysis to frame and testhypotheses 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-networkcollaborations, 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. Byuncovering the correlates of protective immunity, JH-EPICS research will further enhance vaccine design andevaluation of vaccine candidates.