T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination

In 2022, a global mpox outbreak occurred, and remains a concern today. The T cell memory response to MPXV (monkeypox virus) infection has not been fully investigated. In this study, we evaluate this response in convalescent and MVA-BN (Modified Vaccinia Ankara - Bavarian Nordic) vaccinated individuals using VACV-infected cells. Strong CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses are observed, and T cell responses are biased towards viral early expressed proteins. We identify seven immunodominant HLA-A*02:01 restricted MPXV-specific epitopes and focus our detailed phenotypic and scRNAseq analysis on the immunodominant HLA-A*02:01-G5R<sub>18-26</sub>-specific CD8<sup>+</sup> T cell response. While tetramer<sup>+</sup>CD8<sup>+</sup> T cells share similar differentiation and activation phenotypes, T cells from convalescent individuals show greater cytotoxicity, migratory potential to site of infection and TCR clonal expansion. Our data suggest that effective functional profiles of MPXV-specific memory T cells induced by Mpox infection may have an implication on the long-term protective responses to future infection.

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Publication Details

Journal
Nature Communications
Published
2025-05-10
DOI
https://doi.org/10.1038/s41467-025-59370-5
Citations
6
Primary Topic
Poxvirus research and outbreaks
Type
article
Field-Weighted Citation Impact
6.22
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article

T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination

Adam Bates, Alexis Espinosa, Olivia Bird, Yongxu Lu et al.
6 citations
Nature Communications
Poxvirus research and outbreaks
6.22
article

T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination

Adam Bates, Alexis Espinosa, Olivia Bird, Yongxu Lu, Brian Angus, Junyuan Wang, Sally Beer, Elie Antoun, M Pidoux, J. Kenneth Baillie, Deshni Jayathilaka, Malcolm Gracie Semple, Ji-Li Chen, Philip G. Drennan, Zixi Yin, Beibei Wang, Xuan Yao, Guihai Liu
article en
6 citations

Abstract

In 2022, a global mpox outbreak occurred, and remains a concern today. The T cell memory response to MPXV (monkeypox virus) infection has not been fully investigated. In this study, we evaluate this response in convalescent and MVA-BN (Modified Vaccinia Ankara - Bavarian Nordic) vaccinated individuals using VACV-infected cells. Strong CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses are observed, and T cell responses are biased towards viral early expressed proteins. We identify seven immunodominant HLA-A*02:01 restricted MPXV-specific epitopes and focus our detailed phenotypic and scRNAseq analysis on the immunodominant HLA-A*02:01-G5R<sub>18-26</sub>-specific CD8<sup>+</sup> T cell response. While tetramer<sup>+</sup>CD8<sup>+</sup> T cells share similar differentiation and activation phenotypes, T cells from convalescent individuals show greater cytotoxicity, migratory potential to site of infection and TCR clonal expansion. Our data suggest that effective functional profiles of MPXV-specific memory T cells induced by Mpox infection may have an implication on the long-term protective responses to future infection.

Nature CommunicationsVol. 16(1)
National Health Service (GB), Centre National de la Recherche Scientifique (FR), Nottingham University Hospitals NHS Trust (GB), Centre for Human Genetics (GB), Roslin Institute (GB), University of Liverpool (GB), Imperial College Healthcare NHS Trust (GB), Inserm (FR), King's College London (GB), Liverpool School of Tropical Medicine (GB), Guy's and St Thomas' NHS Foundation Trust (GB), University of Cambridge (GB), Manchester Academic Health Science Centre (GB), Western General Hospital (GB), NHS Greater Glasgow and Clyde (GB), Nuffield Orthopaedic Centre (GB), Royal Liverpool University Hospital (GB), Edinburgh Royal Infirmary (GB), Walton Centre (GB), Clatterbridge Cancer Centre NHS Foundation Trust (GB), University of Manchester (GB), Public Health England (GB), University of Oxford (GB), NIHR Oxford Musculoskeletal Biomedical Research Centre (GB), Medawar Building for Pathogen Research (GB), Lung Institute (US), MRC Weatherall Institute of Molecular Medicine (GB), Public Health Scotland (GB), St Mary's Hospital (GB), MRC Human Immunology Unit (GB), Science Oxford (GB), MRC University of Glasgow Centre for Virus Research (GB), Oxford University Hospitals NHS Trust (GB), McGill University and Génome Québec Innovation Centre (CA), Centre for Inflammation Research (GB), King's College Hospital (GB), Queen Elizabeth University Hospital (GB), Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool (GB), European Genomic Institute for Diabetes (FR), University College London (GB), Imperial College London (GB), University of Birmingham (GB), University of Sheffield (GB), University of Edinburgh (GB)
Good health and well-being
Openalex Percentile: Top 4%
Poxvirus research and outbreaks
6.22
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