AUTHOR=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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1369436

DOI=10.3389/fimmu.2024.1369436

ISSN=1664-3224

ABSTRACT=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.