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

Author

Listed:
  • Jenna M. Benoit

    (McMaster University
    McMaster Immunology Research Centre
    St. Joseph’s Healthcare)

  • Jessica A. Breznik

    (McMaster University
    McMaster Immunology Research Centre
    McMaster University)

  • Ying Wu

    (McMaster University
    McMaster Immunology Research Centre)

  • Allison Kennedy

    (McMaster University
    McMaster Immunology Research Centre)

  • Li-Min Liu

    (McMaster University
    McMaster Immunology Research Centre)

  • Braeden Cowbrough

    (McMaster University
    McMaster Immunology Research Centre)

  • Barbara Baker

    (McMaster University)

  • Megan Hagerman

    (McMaster University
    McMaster Immunology Research Centre)

  • Catherine M. Andary

    (McMaster University
    McMaster Immunology Research Centre)

  • Maha Mushtaha

    (McMaster University and Hamilton Health Sciences)

  • Nora Abdalla

    (McMaster University and Hamilton Health Sciences)

  • Jamie D. McNicol

    (McMaster University
    McMaster Immunology Research Centre)

  • Gail Gauvreau

    (McMaster University)

  • Paul Y. Kim

    (McMaster University
    McMaster University)

  • Judah A. Denburg

    (McMaster University)

  • Andrew P. Costa

    (McMaster University
    McMaster University)

  • Darryl P. Leong

    (McMaster University
    McMaster University and Hamilton Health Sciences)

  • Ishac Nazy

    (McMaster University)

  • MyLinh Duong

    (McMaster University
    St. Joseph’s Healthcare
    McMaster University
    McMaster University and Hamilton Health Sciences)

  • Jonathan L. Bramson

    (McMaster University
    McMaster Immunology Research Centre)

  • Maggie J. Larché

    (McMaster University
    McMaster Immunology Research Centre)

  • Chris P. Verschoor

    (McMaster University
    Health Sciences North Research Institute)

  • Dawn M. E. Bowdish

    (McMaster University
    McMaster Immunology Research Centre
    St. Joseph’s Healthcare
    McMaster University)

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.

Suggested Citation

  • 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. McNic, 2025. "No evidence of immune exhaustion after repeated SARS-CoV-2 vaccination in vulnerable and healthy populations," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60216-3
    DOI: 10.1038/s41467-025-60216-3
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