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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)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Covid-19 ; Sars-cov-2 ; T Cell Response ; High Through Put ; Interferon Gamma Release Assay (igra)
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Journal Frontiers in Immunology
Quellenangaben Volume: 12, Issue: , Pages: , Article Number: 688436 Supplement: ,
Publisher Frontiers
Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Unit for Clinical Pharmacology (KKG-EKLiP)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
Immune Response and Infection
PSP Element(s) G-503800-001
G-522100-001
Grants 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
DOI 10.3389/fimmu.2021.688436
WOS ID WOS:000657293400001
Scopus ID 85107223614
PubMed ID 34093595
Erfassungsdatum 2021-07-01
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