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

Ji-Li Chen, Beibei Wang, Yongxu Lu, Elie Antoun, Olivia Bird, Philip G. Drennan, Zixi Yin, Guihai Liu, Xuan Yao, Maya Pidoux, Adam Bates, Deshni Jayathilaka, Junyuan Wang, Brian Angus, Sally Beer, Alexis Espinosa, J. Kenneth Baillie, Malcolm G. Semple, Timothy Rostron, Craig Waugh, Paul Sopp, Julian C. Knight, James N. Fullerton, Mark Coles, Geoffrey L. Smith, Alexander J. Mentzer, Yanchun Peng and Tao Dong ()
Additional contact information
Ji-Li Chen: University of Oxford
Beibei Wang: University of Oxford
Yongxu Lu: University of Oxford
Elie Antoun: University of Oxford
Olivia Bird: Oxford University Hospitals NHS Foundation Trust
Philip G. Drennan: Oxford University Hospitals NHS Foundation Trust
Zixi Yin: University of Oxford
Guihai Liu: University of Oxford
Xuan Yao: University of Oxford
Maya Pidoux: University of Oxford
Adam Bates: University of Oxford
Deshni Jayathilaka: University of Oxford
Junyuan Wang: University of Oxford
Brian Angus: University of Oxford
Sally Beer: Oxford University Hospitals NHS Foundation Trust
Alexis Espinosa: Oxford University Hospitals NHS Foundation Trust
J. Kenneth Baillie: University of Edinburgh
Malcolm G. Semple: University of Liverpool
Timothy Rostron: University of Oxford
Craig Waugh: University of Oxford
Paul Sopp: University of Oxford
Julian C. Knight: University of Oxford
James N. Fullerton: Oxford University Hospitals NHS Foundation Trust
Mark Coles: University of Oxford
Geoffrey L. Smith: University of Oxford
Alexander J. Mentzer: University of Oxford
Yanchun Peng: University of Oxford
Tao Dong: University of Oxford

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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+ and CD4+ 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-G5R18-26-specific CD8+ T cell response. While tetramer+CD8+ 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.

Date: 2025
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DOI: 10.1038/s41467-025-59370-5

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