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

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

Chen, Ji-Li; Wang, Beibei; Lu, Yongxu; Antoun, Elie; Bird, Olivia; Drennan, Philip G; Yin, Zixi; Liu, Guihai; Yao, Xuan; Pidoux, Maya; Bates, Adam; Jayathilaka, Deshni; Wang, Junyuan; Angus, Brian; Beer, Sally; Espinosa, Alexis; Baillie, J Kenneth; Semple, Malcolm G; Rostron, Timothy; Waugh, Craig; Sopp, Paul; Knight, Julian C; Fullerton, James N; Coles, Mark; Smith, Geoffrey L; Mentzer, Alexander J; Peng, Yanchun; Dong, Tao
Nature communications 2025 Vol. 16 pp. 4362
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chen2025t

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-G5R-specific CD8 T cell response. While tetramerCD8 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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