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Principal Investigator: ANDREA L COX
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $759,945
Funding agency: National Cancer Institute
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.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Ab-dependent cellular cytotoxicity><Age><Antibodies><Antibody Response><Antigens><BSL-3 facility><BSL3 facility><Biometrics><Biometry><Biostatistics><COVID disease severity><COVID infected patient><COVID patient><COVID positive patient><COVID severity><COVID-19><COVID-19 antibody><COVID-19 disease severity><COVID-19 immune response><COVID-19 immunity><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 severity><COVID-19 virus><COVID-19 virus infection><COVID19 disease severity><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 severity><COVID19 virus><CV-19><Cell Body><Cell surface><Cells><Class Switching><Class Switchings><Clinical><CoV-2><CoV2><Collaborations><Complement><Complement Proteins><Coronavirus Infectious Disease 2019><Development><Differences between sexes><Differs between sexes><Disease><Disorder><ELISA><Ensure><Enzyme-Linked Immunosorbent Assay><Epidemiology><Ethnic Origin><Ethnicity><Evaluation><Fixation><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Gender><Goals><Health><Human><Immune><Immune response><Immunes><Immunity><Immunoglobulin Class Switching><Immunoglobulin Class Switchings><Immunological response><Infection><Inflammasome><Inflammatory Response><Interdisciplinary Research><Interdisciplinary Study><Isotype Switching><Isotype Switchings><Leadership><Mediating><Metabolic><Methods><Modern Man><Multidisciplinary Collaboration><Multidisciplinary Research><Myeloid-derived suppressor cells><Outcome><PBMC><Pathogenesis><Pathologic><Pathology><Peripheral Blood Mononuclear Cell><Population><Probabilistic Models><Probability Models><Proteins><R-Series Research Projects><R01 Mechanism><R01 Program><Race><Races><Reagent><Regimen><Research><Research Grants><Research Project Grants><Research Projects><Research Resources><Resources><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 antibody><SARS-CoV-2 disease severity><SARS-CoV-2 immune response><SARS-CoV-2 immunity><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 severity><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Science><Serology><Serology test><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 immune response><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Sex Differences><Sexual differences><Staining method><Stains><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Statistical Models><Surrogate Markers><T-Cells><T-Lymphocyte><Testing><Training><Vaccine Design><Viral><Virus><Wuhan coronavirus><age associated difference><age based difference><age dependent difference><age dependent variation><age difference><age related difference><age related variation><age specific difference><ages><antibody against COVID-19><antibody against SARS-CoV-2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody dependent cell mediated cytotoxicity><antibody dependent cytotoxicity><antibody mediated cellular cytotoxicity><antibody to COVID-19><antibody to SARS-CoV-2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antibody-dependent cell cytotoxicity><antibody-dependent cellular cytotoxicity><antibody-mediated cytotoxicity><biosafety level 3 facility><co-morbid><co-morbidity><comorbidity><complementation><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 disease severity><coronavirus disease 2019 immune response><coronavirus disease 2019 immunity><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 severity><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease severity><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><current pandemic><developmental><differ by age><difference across age><difference in age><differences due to race><differences in race><differs by race><differs in race><disease severity><enzyme linked immunoassay><epidemiologic><epidemiological><evaluate vaccines><experiment><experimental research><experimental study><experiments><flow cytophotometry><gender difference><gender-associated difference><hCoV19><host response><immune system response><immunity against COVID-19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunogen><immunoresponse><immunosuppressive myeloid cells><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innate immune sensing><insight><intersectionalities><intersectionality><myeloid suppressor cells><myeloid-derived suppressive cells><nCoV2><neutralizing antibody><new drug target><new druggable target><new marker><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel biomarker><novel drug target><novel druggable target><novel marker><novel pharmacotherapy target><novel therapeutic target><novel therapy target><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><present pandemic><race based differences><race differences><race related differences><racial><racial background><racial difference><racial origin><racially different><sample fixation><serology assay><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 severity><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><single cell analysis><statistical analysis><statistical linear mixed models><statistical linear models><suppressive myeloid cells><surrogate bio-markers><surrogate biomarkers><therapeutic evaluation><therapeutic testing><thymus derived lymphocyte><vaccine candidate><vaccine evaluation><vaccine screening><vaccine testing><variation by age><virology>