Frontiers in Immunology (May 2021)
Broad T Cell Targeting of Structural Proteins After SARS-CoV-2 Infection: High Throughput Assessment of T Cell Reactivity Using an Automated Interferon Gamma Release Assay
- Isabel Brand,
- Isabel Brand,
- Leonard Gilberg,
- Leonard Gilberg,
- Jan Bruger,
- Mercè Garí,
- Andreas Wieser,
- Andreas Wieser,
- Tabea M. Eser,
- Tabea M. Eser,
- Jonathan Frese,
- Mohamed I. M. Ahmed,
- Mohamed I. M. Ahmed,
- Raquel Rubio-Acero,
- Jessica M. Guggenbuehl Noller,
- Noemi Castelletti,
- Jana Diekmannshemke,
- Jana Diekmannshemke,
- Sophie Thiesbrummel,
- Sophie Thiesbrummel,
- Duc Huynh,
- Simon Winter,
- Inge Kroidl,
- Inge Kroidl,
- Christiane Fuchs,
- Christiane Fuchs,
- Christiane Fuchs,
- Michael Hoelscher,
- Michael Hoelscher,
- Michael Hoelscher,
- Julia Roider,
- Julia Roider,
- Sebastian Kobold,
- Sebastian Kobold,
- Sebastian Kobold,
- Michael Pritsch,
- Michael Pritsch,
- Christof Geldmacher,
- Christof Geldmacher
Affiliations
- Isabel Brand
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Isabel Brand
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
- Leonard Gilberg
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Leonard Gilberg
- Department of Infectious Diseases, University Hospital, LMU Munich, Munich, Germany
- Jan Bruger
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Mercè Garí
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health (HMGU), Neuherberg, Germany
- Andreas Wieser
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Andreas Wieser
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Tabea M. Eser
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Tabea M. Eser
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Jonathan Frese
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Mohamed I. M. Ahmed
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Mohamed I. M. Ahmed
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Raquel Rubio-Acero
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Jessica M. Guggenbuehl Noller
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Noemi Castelletti
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Jana Diekmannshemke
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health (HMGU), Neuherberg, Germany
- Jana Diekmannshemke
- Faculty of Business Administration and Economics, Bielefeld University, Bielefeld, Germany
- Sophie Thiesbrummel
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health (HMGU), Neuherberg, Germany
- Sophie Thiesbrummel
- Faculty of Business Administration and Economics, Bielefeld University, Bielefeld, Germany
- Duc Huynh
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
- Simon Winter
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Inge Kroidl
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Inge Kroidl
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Christiane Fuchs
- Institute of Computational Biology, Helmholtz Zentrum München – German Research Center for Environmental Health (HMGU), Neuherberg, Germany
- Christiane Fuchs
- Faculty of Business Administration and Economics, Bielefeld University, Bielefeld, Germany
- Christiane Fuchs
- Center for Mathematics, Technische Universität München, Garching, Germany
- Michael Hoelscher
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Michael Hoelscher
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Michael Hoelscher
- Center for International Health (CIH), University Hospital, LMU Munich, Munich, Germany
- Julia Roider
- Department of Infectious Diseases, University Hospital, LMU Munich, Munich, Germany
- Julia Roider
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Sebastian Kobold
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
- Sebastian Kobold
- German Center for Translational Cancer Research (DKTK), Partner Site Munich, Munich, Germany
- Sebastian Kobold
- 0Unit for Clinical Pharmacology (EKLiP), Helmholtz Zentrum München – German Research Center for Environmental Health (HMGU), Neuherberg, Germany
- Michael Pritsch
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Michael Pritsch
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Christof Geldmacher
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- Christof Geldmacher
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- DOI
- https://doi.org/10.3389/fimmu.2021.688436
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundAdaptive immune responses to structural proteins of the virion play a crucial role in protection against coronavirus disease 2019 (COVID-19). We therefore studied T cell responses against multiple SARS-CoV-2 structural proteins in a large cohort using a simple, fast, and high-throughput approach.MethodsAn automated interferon gamma release assay (IGRA) for the Nucleocapsid (NC)-, Membrane (M)-, Spike-C-terminus (SCT)-, and N-terminus-protein (SNT)-specific T cell responses was performed using fresh whole blood from study subjects with convalescent, confirmed COVID-19 (n = 177, more than 200 days post infection), exposed household members (n = 145), and unexposed controls (n = 85). SARS-CoV-2-specific antibodies were assessed using Elecsys® Anti-SARS-CoV-2 (Ro-N-Ig) and Anti-SARS-CoV-2-ELISA (IgG) (EI-S1-IgG).Results156 of 177 (88%) previously PCR confirmed cases were still positive by Ro-N-Ig more than 200 days after infection. In T cells, most frequently the M-protein was targeted by 88% seropositive, PCR confirmed cases, followed by SCT (85%), NC (82%), and SNT (73%), whereas each of these antigens was recognized by less than 14% of non-exposed control subjects. Broad targeting of these structural virion proteins was characteristic of convalescent SARS-CoV-2 infection; 68% of all seropositive individuals targeted all four tested antigens. Indeed, anti-NC antibody titer correlated loosely, but significantly with the magnitude and breadth of the SARS-CoV-2-specific T cell response. Age, sex, and body mass index were comparable between the different groups.ConclusionSARS-CoV-2 seropositivity correlates with broad T cell reactivity of the structural virus proteins at 200 days after infection and beyond. The SARS-CoV-2-IGRA can facilitate large scale determination of SARS-CoV-2-specific T cell responses with high accuracy against multiple targets.
Keywords