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.

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

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.

Informations de copyright

Copyright © 2021 Brand, Gilberg, Bruger, Garí, Wieser, Eser, Frese, Ahmed, Rubio-Acero, Guggenbuehl Noller, Castelletti, Diekmannshemke, Thiesbrummel, Huynh, Winter, Kroidl, Fuchs, Hoelscher, Roider, Kobold, Pritsch and Geldmacher.

Déclaration de conflit d'intérêts

MP reports grant and non-financial support from Bavarian Ministry for Science and the Arts, non-financial support from Euroimmun, and non-financial support from Roche, during the conduct of the study. JB reports grant and non-financial support from Bavarian Ministry for Science and the Arts. IB and LG report non-financial support from Euroimmun. AW reports personal fees and non-financial support from Roche Diagnostics, non-financial support from Euroimmun, non-financial support from Viramed, non-financial support from Mikrogen, grants, non-financial support and other from German Center for Infection Research DZIF, grants and non-financial support from Government of Bavaria, non-financial support from BMW, non-financial support from Munich Police, from LGL, non-financial support and other from Accenture, during the conduct of the study; non-financial support and other from Bielefeld University, non-financial support and other from Bonn University, non-financial support and other from Helmholtz München, non-financial support and other from Bundeswehr (German army), personal fees and non-financial support from Dr.Box-Betrobox, non-financial support from Dr. Becker MVZ, outside the submitted work; In addition, AW has a patent Sample System for Diagnostics of SARS-CoV-2 pending to Wieser, Hoelscher, Becker. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.