Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein. / Sheetikov, Saveliy A.; Khmelevskaya, Alexandra A.; Zornikova, Ksenia V. et al.
In: Frontiers in Immunology, Vol. 15, 1369436, 22.04.2024.Research output: Contribution to journal › Article › peer-review
}
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 -
ID: 61254070