Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals

Abstract Objectives Vaccine‐induced protective immunity against SARS‐CoV‐2 has proved difficult to sustain. Robust T‐cell responses are thought to play an important role, but T‐cell responses against the SARS‐CoV‐2 spike protein (S‐protein), the core vaccine antigen, following vaccination or natural...

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Main Authors: Daniel J Browne, Pauline Crooks, Corey Smith, Denise L Doolan
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Clinical & Translational Immunology
Subjects:
Online Access:https://doi.org/10.1002/cti2.70031
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author Daniel J Browne
Pauline Crooks
Corey Smith
Denise L Doolan
author_facet Daniel J Browne
Pauline Crooks
Corey Smith
Denise L Doolan
author_sort Daniel J Browne
collection DOAJ
description Abstract Objectives Vaccine‐induced protective immunity against SARS‐CoV‐2 has proved difficult to sustain. Robust T‐cell responses are thought to play an important role, but T‐cell responses against the SARS‐CoV‐2 spike protein (S‐protein), the core vaccine antigen, following vaccination or natural infection are incompletely understood. Methods Herein, the reactivity of 170 putative SARS‐CoV‐2 S‐protein CD8+ and CD4+ T‐cell peptide epitopes in the same individuals prior to vaccination, after COVID‐19 vaccination, and again following subsequent natural infection was assayed using a high‐throughput reverse transcription‐quantitative PCR (HTS‐RT‐qPCR) assay. Results The profile of immunoreactive SARS‐CoV‐2 S‐protein epitopes differed between vaccination and natural infection. Vaccine‐induced immunoreactive epitopes were localised primarily into two extra‐domanial regions. In contrast, epitopes recognised following natural infection were spread across the antigen. Furthermore, T‐cell epitopes in naïve individuals were primarily recognised in association with HLA‐A, while natural infection shifted epitope associations towards HLA‐B, particularly the B7 supertype. Conclusion This study provides insight into T‐cell responses against the SARS‐CoV‐2 S‐protein following vaccination and subsequent natural infection.
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spelling doaj-art-708c0bfecfea40f8acfbab6c9bc645c62025-07-18T05:56:05ZengWileyClinical & Translational Immunology2050-00682025-01-01145n/an/a10.1002/cti2.70031Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individualsDaniel J Browne0Pauline Crooks1Corey Smith2Denise L Doolan3Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine James Cook University Cairns QLD AustraliaQIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology QIMR Berghofer Medical Research Institute Brisbane QLD AustraliaQIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory, Department of Immunology QIMR Berghofer Medical Research Institute Brisbane QLD AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine James Cook University Cairns QLD AustraliaAbstract Objectives Vaccine‐induced protective immunity against SARS‐CoV‐2 has proved difficult to sustain. Robust T‐cell responses are thought to play an important role, but T‐cell responses against the SARS‐CoV‐2 spike protein (S‐protein), the core vaccine antigen, following vaccination or natural infection are incompletely understood. Methods Herein, the reactivity of 170 putative SARS‐CoV‐2 S‐protein CD8+ and CD4+ T‐cell peptide epitopes in the same individuals prior to vaccination, after COVID‐19 vaccination, and again following subsequent natural infection was assayed using a high‐throughput reverse transcription‐quantitative PCR (HTS‐RT‐qPCR) assay. Results The profile of immunoreactive SARS‐CoV‐2 S‐protein epitopes differed between vaccination and natural infection. Vaccine‐induced immunoreactive epitopes were localised primarily into two extra‐domanial regions. In contrast, epitopes recognised following natural infection were spread across the antigen. Furthermore, T‐cell epitopes in naïve individuals were primarily recognised in association with HLA‐A, while natural infection shifted epitope associations towards HLA‐B, particularly the B7 supertype. Conclusion This study provides insight into T‐cell responses against the SARS‐CoV‐2 S‐protein following vaccination and subsequent natural infection.https://doi.org/10.1002/cti2.70031COVID‐19 vaccinesHLA‐B7 antigenSARS‐CoV‐2spike glycoproteinT‐cell epitopesT‐lymphocyte
spellingShingle Daniel J Browne
Pauline Crooks
Corey Smith
Denise L Doolan
Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
Clinical & Translational Immunology
COVID‐19 vaccines
HLA‐B7 antigen
SARS‐CoV‐2
spike glycoprotein
T‐cell epitopes
T‐lymphocyte
title Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
title_full Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
title_fullStr Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
title_full_unstemmed Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
title_short Differential reactivity of SARS‐CoV‐2 S‐protein T‐cell epitopes in vaccinated versus naturally infected individuals
title_sort differential reactivity of sars cov 2 s protein t cell epitopes in vaccinated versus naturally infected individuals
topic COVID‐19 vaccines
HLA‐B7 antigen
SARS‐CoV‐2
spike glycoprotein
T‐cell epitopes
T‐lymphocyte
url https://doi.org/10.1002/cti2.70031
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AT paulinecrooks differentialreactivityofsarscov2sproteintcellepitopesinvaccinatedversusnaturallyinfectedindividuals
AT coreysmith differentialreactivityofsarscov2sproteintcellepitopesinvaccinatedversusnaturallyinfectedindividuals
AT deniseldoolan differentialreactivityofsarscov2sproteintcellepitopesinvaccinatedversusnaturallyinfectedindividuals