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

J Ji-Li Chen B Beibei Wang Y Yongxu Lu E Elie Antoun O Olivia Bird P Philip G. Drennan Z Zixi Yin G Guihai Liu X Xuan Yao (School of Physical Science and Technology, Shanghai Key Laboratory of High-Resolution Electron Microscopy, State Key Laboratory of Advanced Medical Materials and Devices) M Maya Pidoux A Adam Bates D Deshni Jayathilaka J Junyuan Wang B Brian Angus (Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom) S Sally Beer A Alexis Espinosa J J. Kenneth Baillie M Malcolm G. Semple P Peter JM Openshaw B Beatrice Alex P Petros Andrikopoulos B Benjamin Bach W Wendy S. Barclay D Debby Bogaert M Meera Chand (UK Health Security Agency, Canary Wharf) K Kanta Chechi G Graham S. Cooke A Ana da Silva Filipe T Thushan de Silva A Annemarie B. Docherty G Gonçalo dos Santos Correia M Marc-Emmanuel Dumas J Jake Dunning T Tom Fletcher C Christoper A. Green W William Greenhalf J Julian L. Griffin R Rishi K. Gupta E Ewen M. Harrison A Antonia Y. W. Ho K Karl Holden P Peter W. Horby S Samreen Ijaz S Saye Khoo P Paul Klenerman (Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, United Kingdom) A Andrew Law M Matthew R. Lewis S Sonia Liggi W Wei Shen Lim L Lynn Maslen L Laura Merson A Alison M. Meynert S Shona C. Moore M Mahdad Noursadeghi M Michael Olanipekun A Anthonia Osagie M Massimo Palmarini (Medical Research Council-University of Glasgow Centre for Virus Research) C Carlo Palmieri W William A. Paxton G Georgios Pollakis N Nicholas Price A Andrew Rambaut D David L. Robertson C Clark D. Russell V Vanessa Sancho-Shimizu C Caroline J. Sands J Janet T. Scott L Louise Sigfrid T Tom Solomon S Shiranee Sriskandan D David Stuart C Charlotte Summers O Olivia V. Swann Z Zoltan Takats (Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London) P Panteleimon Takis R Richard S. Tedder A A. A. Roger Thompson (Division of Clinical Medicine, University of Sheffield) E Emma C. Thomson R Ryan S. Thwaites (National Heart and Lung Institute, Imperial College London) L Lance CW Turtle M Maria Zambon T Thomas M. Drake C Cameron J. Fairfield S Stephen R. Knight K Kenneth A. Mclean D Derek Murphy L Lisa Norman R Riinu Pius C Catherine A. Shaw M Marie Connor J Jo Dalton C Carrol Gamble (Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, United Kingdom) M Michelle Girvan S Sophie Halpin J Janet Harrison C Clare Jackson J James Lee (Laboratory of Membrane Biophysics and Biology, The Rockefeller University) L Laura Marsh D Daniel Plotkin S Stephanie Roberts E Egle Saviciute S Sara Clohisey R Ross Hendry S Susan Knight G Gary Leeming L Lucy Norris J James Scott-Brown S Sarah Tait M Murray Wham G Gail Carson T Tassos Grammatikopoulos S Sarah E. McDonald V Victoria Shaw S Seán Keating C Cara Donegan R Rebecca G. Spencer C Chloe Donohue F Fiona Griffiths H Hayley Hardwick W Wilna Oosthuyzen T Timothy Rostron C Craig Waugh P Paul Sopp J Julian C. Knight J James N. Fullerton M Mark Coles G Geoffrey L. Smith A Alexander J. Mentzer (Centre for Human Genetics, University of Oxford, Oxford, United Kingdom) Y Yanchun Peng T Tao Dong (Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology)

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published May 10, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (130)

J

Ji-Li Chen

B

Beibei Wang

Y

Yongxu Lu

E

Elie Antoun

O

Olivia Bird

P

Philip G. Drennan

Z

Zixi Yin

G

Guihai Liu

X

Xuan Yao

School of Physical Science and Technology, Shanghai Key Laboratory of High-Resolution Electron Microscopy, State Key Laboratory of Advanced Medical Materials and Devices

M

Maya Pidoux

A

Adam Bates

D

Deshni Jayathilaka

J

Junyuan Wang

B

Brian Angus

Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

S

Sally Beer

A

Alexis Espinosa

J

J. Kenneth Baillie

M

Malcolm G. Semple

P

Peter JM Openshaw

B

Beatrice Alex

P

Petros Andrikopoulos

B

Benjamin Bach

W

Wendy S. Barclay

D

Debby Bogaert

M

Meera Chand

UK Health Security Agency, Canary Wharf

K

Kanta Chechi

G

Graham S. Cooke

A

Ana da Silva Filipe

T

Thushan de Silva

A

Annemarie B. Docherty

G

Gonçalo dos Santos Correia

M

Marc-Emmanuel Dumas

J

Jake Dunning

T

Tom Fletcher

C

Christoper A. Green

W

William Greenhalf

J

Julian L. Griffin

R

Rishi K. Gupta

E

Ewen M. Harrison

A

Antonia Y. W. Ho

K

Karl Holden

P

Peter W. Horby

S

Samreen Ijaz

S

Saye Khoo

P

Paul Klenerman

Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, United Kingdom

A

Andrew Law

M

Matthew R. Lewis

S

Sonia Liggi

W

Wei Shen Lim

L

Lynn Maslen

L

Laura Merson

A

Alison M. Meynert

S

Shona C. Moore

M

Mahdad Noursadeghi

M

Michael Olanipekun

A

Anthonia Osagie

M

Massimo Palmarini

Medical Research Council-University of Glasgow Centre for Virus Research

C

Carlo Palmieri

W

William A. Paxton

G

Georgios Pollakis

N

Nicholas Price

A

Andrew Rambaut

D

David L. Robertson

C

Clark D. Russell

V

Vanessa Sancho-Shimizu

C

Caroline J. Sands

J

Janet T. Scott

L

Louise Sigfrid

T

Tom Solomon

S

Shiranee Sriskandan

D

David Stuart

C

Charlotte Summers

O

Olivia V. Swann

Z

Zoltan Takats

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London

P

Panteleimon Takis

R

Richard S. Tedder

A

A. A. Roger Thompson

Division of Clinical Medicine, University of Sheffield

E

Emma C. Thomson

R

Ryan S. Thwaites

National Heart and Lung Institute, Imperial College London

L

Lance CW Turtle

M

Maria Zambon

T

Thomas M. Drake

C

Cameron J. Fairfield

S

Stephen R. Knight

K

Kenneth A. Mclean

D

Derek Murphy

L

Lisa Norman

R

Riinu Pius

C

Catherine A. Shaw

M

Marie Connor

J

Jo Dalton

C

Carrol Gamble

Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, United Kingdom

M

Michelle Girvan

S

Sophie Halpin

J

Janet Harrison

C

Clare Jackson

J

James Lee

Laboratory of Membrane Biophysics and Biology, The Rockefeller University

L

Laura Marsh

D

Daniel Plotkin

S

Stephanie Roberts

E

Egle Saviciute

S

Sara Clohisey

R

Ross Hendry

S

Susan Knight

G

Gary Leeming

L

Lucy Norris

J

James Scott-Brown

S

Sarah Tait

M

Murray Wham

G

Gail Carson

T

Tassos Grammatikopoulos

S

Sarah E. McDonald

V

Victoria Shaw

S

Seán Keating

C

Cara Donegan

R

Rebecca G. Spencer

C

Chloe Donohue

F

Fiona Griffiths

H

Hayley Hardwick

W

Wilna Oosthuyzen

T

Timothy Rostron

C

Craig Waugh

P

Paul Sopp

J

Julian C. Knight

J

James N. Fullerton

M

Mark Coles

G

Geoffrey L. Smith

A

Alexander J. Mentzer

Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

Y

Yanchun Peng

T

Tao Dong

Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology