Frontiers in Immunology (May 2021)

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

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

DOI
https://doi.org/10.3389/fimmu.2021.688436
Journal volume & issue
Vol. 12

Abstract

Read online

BackgroundAdaptive 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.MethodsAn 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).Results156 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.ConclusionSARS-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.

Keywords