JCI Insight (May 2022)

Immunogenic epitope panel for accurate detection of non-cross-reactive T cell response to SARS-CoV-2

  • Aleksei Titov,
  • Regina Shaykhutdinova,
  • Olga V. Shcherbakova,
  • Yana V. Serdyuk,
  • Savely A. Sheetikov,
  • Ksenia V. Zornikova,
  • Alexandra V. Maleeva,
  • Alexandra Khmelevskaya,
  • Dmitry V. Dianov,
  • Naina T. Shakirova,
  • Dmitry B. Malko,
  • Maxim Shkurnikov,
  • Stepan Nersisyan,
  • Alexander Tonevitsky,
  • Ekaterina Khamaganova,
  • Anton V. Ershov,
  • Elena Y. Osipova,
  • Ruslan V. Nikolaev,
  • Dmitry E. Pershin,
  • Viktoria A. Vedmedskia,
  • Michael Maschan,
  • Victoria R. Ginanova,
  • Grigory A. Efimov

Journal volume & issue
Vol. 7, no. 9

Abstract

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The ongoing COVID-19 pandemic calls for more effective diagnostic tools. T cell response assessment serves as an independent indicator of prior COVID-19 exposure while also contributing to a more comprehensive characterization of SARS-CoV-2 immunity. In this study, we systematically assessed the immunogenicity of 118 epitopes with immune cells collected from multiple cohorts of vaccinated, convalescent, healthy unexposed, and SARS-CoV-2–exposed donors. We identified 75 immunogenic epitopes, 24 of which were immunodominant. We further confirmed HLA restriction for 49 epitopes and described association with more than 1 HLA allele for 14 of these. Exclusion of 2 cross-reactive epitopes that generated a response in prepandemic samples left us with a 73-epitope set that offered excellent diagnostic specificity without losing sensitivity compared with full-length antigens, and this evoked a robust cross-reactive response. We subsequently incorporated this set of epitopes into an in vitro diagnostic Corona-T-test, which achieved a diagnostic accuracy of 95% in a clinical trial. In a cohort of asymptomatic seronegative individuals with a history of prolonged SARS-CoV-2 exposure, we observed a complete absence of T cell response to our epitope panel. In combination with strong reactivity to full-length antigens, this suggests that a cross-reactive response might protect these individuals.

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