Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein

Sheetikov, S.A.; Khmelevskaya, A.A.; Zornikova, K.V.; Zvyagin, I.V.; Shomuradova, A.S.; Serdyuk, Y.V.; Shakirova, N.T.; Peshkova, I.O.; Titov, A.; Romaniuk, D.S.; Shagina, I.A.; Chudakov, D.M.; Kiryukhin, D.O.; Shcherbakova, O.V.; Khamaganova, E.G.; Dzutseva, V.; Afanasiev, A.; Bogolyubova, A.V.; Efimov, G.A.

Авторы: Sheetikov Saveliy A., Khmelevskaya Alexandra A., Zornikova Ksenia V., Zvyagin Ivan V., Shomuradova Alina S., Serdyuk Yana V., Shakirova Naina T., Peshkova Iuliia O., Titov Aleksei, Romaniuk Dmitrii S., Shagina Irina A., Chudakov Dmitry M., Kiryukhin Dmitry O., Shcherbakova Olga V., Khamaganova Ekaterina G., Dzutseva Vitalina, Afanasiev Andrei, Bogolyubova Apollinariya V., Efimov Grigory A.
Журнал: Frontiers in immunology
Том: 15
Год издания: 2024
Издательство: Frontiers Research Foundation]
Местоположение издательства: [Lausanne, Switzerland
DOI: 10.3389/fimmu.2024.1369436
Аннотация: Adenovirus vaccines, particularly the COVID-19 Ad5-nCoV adenovirus vaccine, have emerged as promising tools in the fight against infectious diseases. In this study, we investigated the structure of the T cell response to the Spike protein of the SARS-CoV-2 virus used in the COVID-19 Ad5-nCoV adenoviral vaccine in a phase 3 clinical trial (NCT04540419). In 69 participants, we collected peripheral blood samples at four time points after vaccination or placebo injection. Sequencing of T cell receptor repertoires from Spike-stimulated T cell cultures at day 14 from 17 vaccinated revealed a more diverse CD4+ T cell repertoire compared to CD8+. Nevertheless, CD8+ clonotypes accounted for more than half of the Spike-specific repertoire. Our longitudinal analysis showed a peak T cell response at day 14, followed by a decline until month 6. Remarkably, multiple T cell clonotypes persisted for at least 6 months after vaccination, as demonstrated by ex vivo stimulation. Examination of CDR3 regions revealed homologous sequences in both CD4+ and CD8+ clonotypes, with major CD8+ clonotypes sharing high similarity with annotated sequences specific for the NYNYLYRLF peptide, suggesting potential immunodominance. In conclusion, our study demonstrates the immunogenicity of the Ad5-nCoV adenoviral vaccine and highlights its ability to induce robust and durable T cell responses. These findings provide valuable insight into the efficacy of the vaccine against COVID-19 and provide critical information for ongoing efforts to control infectious diseases.
Добавил в систему: Шитиков Савелий Андреевич

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Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike proteinстатья Исследовательская статья