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
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
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Research Article COVID-19 Clinical trials

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

Abstract

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.

Authors

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

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Figure 2

Response to MHC-II peptides differs significantly in Vac and CP donors.

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Response to MHC-II peptides differs significantly in Vac and CP donors. ...
(A) Response to the indicated antigens as measured by ELISpot for Vac (n = 43) and CP (n = 51). A normalized mean of 2 duplicate wells and a median with interquartile range. Mann-Whitney U test (S peptides, P = 0.013; MHC-II peptides, recombinant S protein, P < 0.0001). (B) Volcano plot shows the effect of a particular HLA allele on response to the same peptide sets and antigens. The x axis denotes the decimal logarithm of the ratio of the median response among HLA carriers to that of individuals without the HLA. The y axis denotes the negative decimal logarithm of the P value. The 3 most significant associations are annotated. P = 0.05 is depicted by the dotted line (Fisher’s exact test). (C–E) Receiver operating characteristic (ROC) curves for MHC I + II peptides versus S peptides in Vac versus HD-2019 samples (C); MHC I + II peptides versus S, N, or M peptides in CP versus HD-2019 samples (D); and MHC I + II peptides versus the sum of S, N, and M peptides and versus multiple regression model, incorporating S, N, and M peptides in CP versus HD-2019 samples (E). Three HD-2019 donors with cross-reactive responses were excluded from the ROC analysis for MHC I + II peptides.