TY - JOUR
T1 - T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination
AU - ISARIC4C Investigators
AU - Chen, Ji Li
AU - Wang, Beibei
AU - Lu, Yongxu
AU - Antoun, Elie
AU - Bird, Olivia
AU - Drennan, Philip G.
AU - Yin, Zixi
AU - Liu, Guihai
AU - Yao, Xuan
AU - Pidoux, Maya
AU - Bates, Adam
AU - Jayathilaka, Deshni
AU - Wang, Junyuan
AU - Angus, Brian
AU - Beer, Sally
AU - Espinosa, Alexis
AU - Kenneth Baillie, J.
AU - Semple, Malcolm G.
AU - Rostron, Timothy
AU - Waugh, Craig
AU - Sopp, Paul
AU - Knight, Julian C.
AU - Fullerton, James N.
AU - Coles, Mark
AU - Smith, Geoffrey L.
AU - Mentzer, Alexander J.
AU - Peng, Yanchun
AU - Dong, Tao
AU - Kenneth Baillie, J.
AU - Openshaw, Peter J.M.
AU - Semple, Malcolm G.
AU - Alex, Beatrice
AU - Andrikopoulos, Petros
AU - Bach, Benjamin
AU - Barclay, Wendy S.
AU - Bogaert, Debby
AU - Chand, Meera
AU - Chechi, Kanta
AU - Cooke, Graham S.
AU - Filipe, Ana da Silva
AU - de Silva, Thushan
AU - Docherty, Annemarie B.
AU - Correia, Gonçalo Dos Santos
AU - Dumas, Marc Emmanuel
AU - Dunning, Jake
AU - Fletcher, Tom
AU - Green, Christoper A.
AU - Greenhalf, William
AU - Griffin, Julian L.
AU - Gupta, Rishi K.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/5/10
Y1 - 2025/5/10
N2 - 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 MVABN (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.
AB - 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 MVABN (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.
U2 - 10.1038/s41467-025-59370-5
DO - 10.1038/s41467-025-59370-5
M3 - Article
C2 - 40348752
AN - SCOPUS:105005235690
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4362
ER -
