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

ISARIC4C Investigators; 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; Tao Dong

doi:10.1038/s41467-025-59370-5

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

ISARIC4C Investigators
, 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, Tao Dong

Clinical Sciences

University of Oxford
Oxford University Hospitals NHS Foundation Trust
University of Edinburgh
Royal Infirmary of Edinburgh
University of Liverpool
Imperial College London
Imperial College Healthcare NHS Trust
Digestion and Reproduction
UK Health Security Agency
MRC-University of Glasgow Centre for Virus Research
University of Sheffield
Lille Regional University Hospital Centre
McGill University
University of Birmingham
University College London

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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 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-G5R_18-26-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.

Original language	English
Article number	4362
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-59370-5
Publication status	Published - 10 May 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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ISARIC4C Investigators, Chen, J. L., Wang, B., Lu, Y., Antoun, E., Bird, O., Drennan, P. G., Yin, Z., Liu, G., Yao, X., Pidoux, M., Bates, A., Jayathilaka, D., Wang, J., Angus, B., Beer, S., Espinosa, A., Kenneth Baillie, J., Semple, M. G., ... Dong, T. (2025). T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination. Nature Communications, 16(1), Article 4362. https://doi.org/10.1038/s41467-025-59370-5

@article{37e1fb3ac78f479d83fcce11c347e373,

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

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 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.",

author = "\{ISARIC4C Investigators\} and Chen, \{Ji Li\} and Beibei Wang and Yongxu Lu and Elie Antoun and Olivia Bird and Drennan, \{Philip G.\} and Zixi Yin and Guihai Liu and Xuan Yao and Maya Pidoux and Adam Bates and Deshni Jayathilaka and Junyuan Wang and Brian Angus and Sally Beer and Alexis Espinosa and \{Kenneth Baillie\}, J. and Semple, \{Malcolm G.\} and Timothy Rostron and Craig Waugh and Paul Sopp and Knight, \{Julian C.\} and Fullerton, \{James N.\} and Mark Coles and Smith, \{Geoffrey L.\} and Mentzer, \{Alexander J.\} and Yanchun Peng and Tao Dong and \{Kenneth Baillie\}, J. and Openshaw, \{Peter J.M.\} and Semple, \{Malcolm G.\} and Beatrice Alex and Petros Andrikopoulos and Benjamin Bach and Barclay, \{Wendy S.\} and Debby Bogaert and Meera Chand and Kanta Chechi and Cooke, \{Graham S.\} and Filipe, \{Ana da Silva\} and \{de Silva\}, Thushan and Docherty, \{Annemarie B.\} and Correia, \{Gon{\c c}alo Dos Santos\} and Dumas, \{Marc Emmanuel\} and Jake Dunning and Tom Fletcher and Green, \{Christoper A.\} and William Greenhalf and Griffin, \{Julian L.\} and Gupta, \{Rishi K.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = may,

day = "10",

doi = "10.1038/s41467-025-59370-5",

language = "English",

volume = "16",

journal = "Nature Communications",

issn = "2041-1723",

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ISARIC4C Investigators, Chen, JL, Wang, B, Lu, Y, Antoun, E, Bird, O, Drennan, PG, Yin, Z, Liu, G, Yao, X, Pidoux, M, Bates, A, Jayathilaka, D, Wang, J, Angus, B, Beer, S, Espinosa, A, Kenneth Baillie, J, Semple, MG, Rostron, T, Waugh, C, Sopp, P, Knight, JC, Fullerton, JN, Coles, M, Smith, GL, Mentzer, AJ, Peng, Y & Dong, T 2025, 'T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination', Nature Communications, vol. 16, no. 1, 4362. https://doi.org/10.1038/s41467-025-59370-5

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.

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 -

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

Abstract

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