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Brand, I.* ; Gilberg, L.* ; Bruger, J.* ; Garí, M. ; Wieser, A.* ; Eser, T.M.* ; Frese, J.* ; Ahmed, M.I.M.* ; Rubio-Acero, R.* ; Guggenbüehl Noller, J.M.* ; Castelletti, N.* ; Diekmannshemke, J. ; Thiesbrummel, S. ; Huynh, D.* ; Winter, S.* ; Kroidl, I.* ; Fuchs, C. ; Hoelscher, M.* ; Roider, J.* ; Kobold, S. ; Pritsch, M.* ; Geldmacher, C.*

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.

Front. Immunol. 12:688436 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background: Adaptive 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. Methods: An 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). Results: 156 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. Conclusion: SARS-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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Covid-19 ; Sars-cov-2 ; T Cell Response ; High Through Put ; Interferon Gamma Release Assay (igra)
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 12, Heft: , Seiten: , Artikelnummer: 688436 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Unit for Clinical Pharmacology (KKG-EKLiP)
Förderungen European Union's Horizon 2020 research and innovation programme, ORCHESTRA
Marie-Sklodowska-Curie Program Training Network for the Immunotherapy of Cancer and for Optimizing adoptive T cell therapy of cancer - H2020 Program of the European Union
German Ministry for Education and Research
University of Bielefeld
University of Bonn
Helmholtz Centre Munich
LMU Munich
University Hospital
Bavarian State Ministry of Science and the Arts
Bavarian Ministry for Science and Arts
Hector foundation
International Doctoral Program i Target
Jose-Carreras Foundation
Bavarian Ministry of Economic affairs (m4 award)
Fritz-Bender-Foundation
German Research Foundation (DFG)
European Research Council, ARMOR-T
Bundesministerium fur Bildung und Forschung Project Oncoattract and CONTRACT
LMU Munich's Institutional Strategy LMUexcellent within the German Excellence Initiative
Ernst-Jung-Stiftung
German Cancer Aid
Elite Network of Bavaria
Program for Advancement of Corona Research