期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.688436
关键词
SARS-CoV-2; COVID-19; T cell response; interferon gamma release assay (IGRA); high through put
类别
资金
- Program for Advancement of Corona Research
- Bavarian Ministry for Science and Arts
- Bavarian State Ministry of Science and the Arts
- University Hospital
- LMU Munich
- Helmholtz Centre Munich
- University of Bonn
- University of Bielefeld
- German Ministry for Education and Research [01KI20271]
- 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 [641549, 955575]
- Hector foundation
- International Doctoral Program i Target
- Elite Network of Bavaria
- German Cancer Aid
- Ernst-Jung-Stiftung
- LMU Munich's Institutional Strategy LMUexcellent within the German Excellence Initiative
- Bundesministerium fur Bildung und Forschung Project Oncoattract and CONTRACT
- European Research Council, ARMOR-T [756017]
- German Research Foundation (DFG)
- Fritz-Bender-Foundation
- Bavarian Ministry of Economic affairs (m4 award)
- Jose-Carreras Foundation
- European Union's Horizon 2020 research and innovation programme, ORCHESTRA [101016167]
- European Research Council (ERC) [756017] Funding Source: European Research Council (ERC)
Adaptive immune responses to structural proteins of the SARS-CoV-2 virus play a crucial role in protection against COVID-19. This study found that convalescent COVID-19 patients still exhibit broad T cell reactivity to multiple SARS-CoV-2 structural proteins over 200 days after infection. The study also showed a loose but significant correlation between anti-Nucleocapsid antibody titer and the magnitude and breadth of the T cell response.
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-CoV2-specific antibodies were assessed using Elecsys (R) 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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