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.

Frontiers in immunology 2021

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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. 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). 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. 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. 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.

Citation

Isabel Brand, Leonard Gilberg, Jan Bruger, Mercè Garí, Andreas Wieser, Tabea M Eser, Jonathan Frese, Mohamed I M Ahmed, Raquel Rubio-Acero, Jessica M Guggenbuehl Noller, Noemi Castelletti, Jana Diekmannshemke, Sophie Thiesbrummel, Duc Huynh, Simon Winter, Inge Kroidl, Christiane Fuchs, Michael Hoelscher, Julia Roider, Sebastian Kobold, Michael Pritsch, Christof Geldmacher. 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. Frontiers in immunology. 2021;12:688436