tetano
Editor, Senior Moderator
Front Immunol
. 2024 Apr 2:15:1369436.
doi: 10.3389/fimmu.2024.1369436. eCollection 2024. Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein
Saveliy A Sheetikov[SUP] 1 2 [/SUP], Alexandra A Khmelevskaya[SUP] 1 [/SUP], Ksenia V Zornikova[SUP] 1 2 [/SUP], Ivan V Zvyagin[SUP] 3 4 [/SUP], Alina S Shomuradova[SUP] 1 2 [/SUP], Yana V Serdyuk[SUP] 1 [/SUP], Naina T Shakirova[SUP] 1 [/SUP], Iuliia O Peshkova[SUP] 1 [/SUP], Aleksei Titov[SUP] 1 [/SUP], Dmitrii S Romaniuk[SUP] 1 [/SUP], Irina A Shagina[SUP] 3 4 [/SUP], Dmitry M Chudakov[SUP] 3 4 5 [/SUP], Dmitry O Kiryukhin[SUP] 1 [/SUP], Olga V Shcherbakova[SUP] 1 [/SUP], Ekaterina G Khamaganova[SUP] 1 [/SUP], Vitalina Dzutseva[SUP] 6 7 [/SUP], Andrei Afanasiev[SUP] 7 [/SUP], Apollinariya V Bogolyubova[SUP] 1 [/SUP], Grigory A Efimov[SUP] 1 [/SUP]
Affiliations
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[SUP]+[/SUP] T cell repertoire compared to CD8[SUP]+[/SUP]. Nevertheless, CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] clonotypes, with major CD8[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2; T cell; T cell receptor; TCR sequencing; adenoviral vaccine; spike protein; vaccination.
. 2024 Apr 2:15:1369436.
doi: 10.3389/fimmu.2024.1369436. eCollection 2024. Clonal structure and the specificity of vaccine-induced T cell response to SARS-CoV-2 Spike protein
Saveliy A Sheetikov[SUP] 1 2 [/SUP], Alexandra A Khmelevskaya[SUP] 1 [/SUP], Ksenia V Zornikova[SUP] 1 2 [/SUP], Ivan V Zvyagin[SUP] 3 4 [/SUP], Alina S Shomuradova[SUP] 1 2 [/SUP], Yana V Serdyuk[SUP] 1 [/SUP], Naina T Shakirova[SUP] 1 [/SUP], Iuliia O Peshkova[SUP] 1 [/SUP], Aleksei Titov[SUP] 1 [/SUP], Dmitrii S Romaniuk[SUP] 1 [/SUP], Irina A Shagina[SUP] 3 4 [/SUP], Dmitry M Chudakov[SUP] 3 4 5 [/SUP], Dmitry O Kiryukhin[SUP] 1 [/SUP], Olga V Shcherbakova[SUP] 1 [/SUP], Ekaterina G Khamaganova[SUP] 1 [/SUP], Vitalina Dzutseva[SUP] 6 7 [/SUP], Andrei Afanasiev[SUP] 7 [/SUP], Apollinariya V Bogolyubova[SUP] 1 [/SUP], Grigory A Efimov[SUP] 1 [/SUP]
Affiliations
- PMID: 38629062
- PMCID: PMC11018901
- DOI: 10.3389/fimmu.2024.1369436
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[SUP]+[/SUP] T cell repertoire compared to CD8[SUP]+[/SUP]. Nevertheless, CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] clonotypes, with major CD8[SUP]+[/SUP] 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.
Keywords: SARS-CoV-2; T cell; T cell receptor; TCR sequencing; adenoviral vaccine; spike protein; vaccination.