Architecture of the SARS-CoV-2-specific T cell repertoire

Zornikova, Ksenia V.; Sheetikov, Saveliy Andreevich; Rusinov, Alexander Yu; Iskhakov, Rustam N.; Bogolyubova, Apollinariya V.

doi:10.3389/fimmu.2023.1070077

Cited by 6 publications

(2 citation statements)

References 128 publications

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“…In sarbecovirus infections, as in most viral diseases, several studies have shown that T cells are activated early and are associated with effective viral elimination, as well as affording protection against variants arising during the pandemic. This has been confirmed later in many studies on the landscape of cell-mediated responses to SARS-CoV-2 [2][3][4][5].…”

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confidence: 54%

When Cell-Mediated Immunity after Vaccination Is Important

Paganelli

2024

Pathogens

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confidence: 54%

When Cell-Mediated Immunity after Vaccination Is Important

Paganelli

2024

Pathogens

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“…The magnitude of the T cell response decreases over time differently depending on the immunodominance of the epitope. Initial richness of clonal diversity is critical for prolonged persistence of epitope-specific T cells ( 29 , 30 ).…”

Section: Introductionmentioning

confidence: 99%

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

Sheetikov,

Khmelevskaya,

Zornikova

et al. 2024

Front. Immunol.

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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.

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Robust detection of SARS-CoV-2 exposure in the population using T-cell repertoire profiling

Vlasova,

Nekrasova,

Komkov

et al. 2023

Preprint

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The COVID-19 pandemic clearly demonstrates the need to monitor the spread of infectious diseases and population immunity. Probing adaptive immunity by sequencing the repertoire of antigen receptors (Rep-Seq) encoding specificity and immunological memory has become a method of choice for immunology studies. Rep-Seq can detect the imprint of past and ongoing infections and study individual responses to SARS-CoV-2 as shown in a number of recent studies. Here we apply a machine learning approach to two large datasets with more than 1200 high-quality repertoires from healthy and COVID-19-convalescent donor repertoires to infer T-cell receptor (TCR) repertoire features that were induced by SARS-CoV-2 exposure. Proper standardization of Rep-Seq batches, access to human leukocyte antigen (HLA) typing and both α- and β-chain sequences of TCRs allowed us to generate a high-quality biomarker database and build a robust and highly accurate classifier for COVID-19 exposure applicable to individual TCR repertoires obtained using different protocols, paving a way to Rep-Seq-based immune status assessment in large cohorts of donors.

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Architecture of the SARS-CoV-2-specific T cell repertoire

Cited by 6 publications

References 128 publications

When Cell-Mediated Immunity after Vaccination Is Important

When Cell-Mediated Immunity after Vaccination Is Important

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

Robust detection of SARS-CoV-2 exposure in the population using T-cell repertoire profiling

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