TY - JOUR

T1 - Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein

AU - Sheetikov, Saveliy A.

AU - Khmelevskaya, Alexandra A.

AU - Zornikova, Ksenia V.

AU - Zvyagin, Ivan V.

AU - Shomuradova, Alina S.

AU - Serdyuk, Yana V.

AU - Shakirova, Naina T.

AU - Peshkova, Iuliia O.

AU - Titov, Aleksei

AU - Romaniuk, Dmitrii S.

AU - Shagina, Irina A.

AU - Chudakov, Dmitry M.

AU - Kiryukhin, Dmitry O.

AU - Shcherbakova, Olga V.

AU - Khamaganova, Ekaterina G.

AU - Dzutseva, Vitalina

AU - Afanasiev, Andrei

AU - Bogolyubova, Apollinariya V.

AU - Efimov, Grigory A.

N1 - The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was financially supported by the Russian Science Foundation grant 20-15-00395 (to AB).

PY - 2024/4/22

Y1 - 2024/4/22

N2 - 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.

AB - 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.

KW - SARS-CoV-2

KW - T cell

KW - T cell receptor

KW - TCR sequencing

KW - adenoviral vaccine

KW - spike protein

KW - vaccination

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85190385386&origin=inward&txGid=3cecb02240194b57e312fd832980598a

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001203777400001

UR - https://www.mendeley.com/catalogue/bfec2be9-a108-3783-8ef8-9651187624f7/

U2 - 10.3389/fimmu.2024.1369436

DO - 10.3389/fimmu.2024.1369436

M3 - Article

C2 - 38629062

VL - 15

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1369436

ER -