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Principal Investigator: Jeffrey Cohen
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2021
Award: $11,170
Funding agency: National Institute of Allergy and Infectious Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune response. Assays to detect virus-specific T cells are important to appreciate the role of T cell in controlling COVID-19, and HLA-matched virus-specific T cells might be used to treat immunocompromised persons with this disease and to accelerate virus clearance in these persons to reduce shedding and transmission.
In FY2021 we collaborated with investigators at Childrens National Hospital, Washington, DC, to show that SARS-CoV-2-specific T cells could be isolated and expanded in vitro from persons previously infected with the SARS-CoV-2. We found that these T cells recognize immunodominant viral epitopes in conserved regions of membrane, spike, and nucleocapsid. After expansion of the T cells in vitro using a good manufacturing practice-compliant methodology, we showed that SARS-CoV-2 membrane, spike, and nucleocapsid peptides elicited interferon-gamma production, in 59%, 26%, and 22% of convalescent donors, respectively. We found multiple CD4-restricted T-cell epitopes that were polyfunctional, i.e. that produced multiple cytokines after stimulation with SARS-CoV-2 peptides, within a highly conserved region of membrane protein, These SARS-CoV-2 specific T cells might be useful for prevention or early treatment of SARS-CoV-2 infection in immunocompromised patients.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Antibodies><Antigenic Determinants><Assay><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><COVID-19><COVID-19 infection><COVID-19 virus><COVID19><COVID19 infection><COVID19 virus><CV-19><CV19><Cessation of life><Child><Child Youth><Children (0-21)><CoV-2><CoV2><Death><Disease><Disorder><Early treatment><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Epitopes><Gamma interferon><Goals><Hospitals><Human><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><Immune Interferon><Immune response><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunosuppressed Host><In Vitro><Infection><Interferon Gamma><Interferon Type II><Interferon-gamma><Investigators><Measures><Membrane><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Methodology><Modern Man><Nucleocapsid><Peptides><Persons><Prevalence><Prevention><Production><Research Personnel><Researchers><Role><SARS corona virus 2><SARS-CoV-2><SARS-CoV-2 infection><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><Serology><Serology test><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Surface Proteins><T cell response><T-Cell Epitopes><T-Cells><T-Lymphocyte><T-Lymphocyte Epitopes><Time><Transmission><Viral><Virus><Washington><Wuhan coronavirus><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><cytokine><early therapy><epidemiologic investigation><epidemiology study><hCoV19><host response><immune system response><immunoresponse><immunosuppressed patient><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><lFN-Gamma><membrane structure><nCoV2><respiratory><serology assay><social role><thymus derived lymphocyte><transmission process><youngster>