No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion, which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional...

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Main Authors: Jenna M. Benoit, Jessica A. Breznik, Ying Wu, Allison Kennedy, Li-Min Liu, Braeden Cowbrough, Barbara Baker, Megan Hagerman, Catherine M. Andary, Maha Mushtaha, Nora Abdalla, Jamie D. McNicol, Gail Gauvreau, Paul Y. Kim, Judah A. Denburg, Andrew P. Costa, Darryl P. Leong, Ishac Nazy, MyLinh Duong, Jonathan L. Bramson, Maggie J. Larché, Chris P. Verschoor, Dawn M. E. Bowdish
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60216-3
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author Jenna M. Benoit
Jessica A. Breznik
Ying Wu
Allison Kennedy
Li-Min Liu
Braeden Cowbrough
Barbara Baker
Megan Hagerman
Catherine M. Andary
Maha Mushtaha
Nora Abdalla
Jamie D. McNicol
Gail Gauvreau
Paul Y. Kim
Judah A. Denburg
Andrew P. Costa
Darryl P. Leong
Ishac Nazy
MyLinh Duong
Jonathan L. Bramson
Maggie J. Larché
Chris P. Verschoor
Dawn M. E. Bowdish
author_facet Jenna M. Benoit
Jessica A. Breznik
Ying Wu
Allison Kennedy
Li-Min Liu
Braeden Cowbrough
Barbara Baker
Megan Hagerman
Catherine M. Andary
Maha Mushtaha
Nora Abdalla
Jamie D. McNicol
Gail Gauvreau
Paul Y. Kim
Judah A. Denburg
Andrew P. Costa
Darryl P. Leong
Ishac Nazy
MyLinh Duong
Jonathan L. Bramson
Maggie J. Larché
Chris P. Verschoor
Dawn M. E. Bowdish
author_sort Jenna M. Benoit
collection DOAJ
description Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion, which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada. Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was not associated with increased T cell exhaustion in older frail adults, immunosuppressed individuals, or healthy adults.
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spelling doaj-art-43173b5acc274bf6b7d81cdc830e9a7a2025-08-20T02:37:33ZengNature PortfolioNature Communications2041-17232025-06-0116111410.1038/s41467-025-60216-3No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populationsJenna M. Benoit0Jessica A. Breznik1Ying Wu2Allison Kennedy3Li-Min Liu4Braeden Cowbrough5Barbara Baker6Megan Hagerman7Catherine M. Andary8Maha Mushtaha9Nora Abdalla10Jamie D. McNicol11Gail Gauvreau12Paul Y. Kim13Judah A. Denburg14Andrew P. Costa15Darryl P. Leong16Ishac Nazy17MyLinh Duong18Jonathan L. Bramson19Maggie J. Larché20Chris P. Verschoor21Dawn M. E. Bowdish22Department of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityPopulation Health Research Institute, McMaster University and Hamilton Health SciencesPopulation Health Research Institute, McMaster University and Hamilton Health SciencesDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityMcMaster Institute for Research on Aging, McMaster UniversityDepartment of Medicine, McMaster UniversityMcMaster Centre for Transfusion Research, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityDepartment of Medicine, McMaster UniversityAbstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion, which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada. Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was not associated with increased T cell exhaustion in older frail adults, immunosuppressed individuals, or healthy adults.https://doi.org/10.1038/s41467-025-60216-3
spellingShingle Jenna M. Benoit
Jessica A. Breznik
Ying Wu
Allison Kennedy
Li-Min Liu
Braeden Cowbrough
Barbara Baker
Megan Hagerman
Catherine M. Andary
Maha Mushtaha
Nora Abdalla
Jamie D. McNicol
Gail Gauvreau
Paul Y. Kim
Judah A. Denburg
Andrew P. Costa
Darryl P. Leong
Ishac Nazy
MyLinh Duong
Jonathan L. Bramson
Maggie J. Larché
Chris P. Verschoor
Dawn M. E. Bowdish
No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
Nature Communications
title No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
title_full No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
title_fullStr No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
title_full_unstemmed No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
title_short No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations
title_sort no evidence of immune exhaustion after repeated sars cov 2 vaccination in vulnerable and healthy populations
url https://doi.org/10.1038/s41467-025-60216-3
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