T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination
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
Authors (130)
Ji-Li Chen
Beibei Wang
Yongxu Lu
Elie Antoun
Olivia Bird
Philip G. Drennan
Zixi Yin
Guihai Liu
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
Maya Pidoux
Adam Bates
Deshni Jayathilaka
Junyuan Wang
Brian Angus
Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom
Sally Beer
Alexis Espinosa
J. Kenneth Baillie
Malcolm G. Semple
Peter JM Openshaw
Beatrice Alex
Petros Andrikopoulos
Benjamin Bach
Wendy S. Barclay
Debby Bogaert
Meera Chand
UK Health Security Agency, Canary Wharf
Kanta Chechi
Graham S. Cooke
Ana da Silva Filipe
Thushan de Silva
Annemarie B. Docherty
Gonçalo dos Santos Correia
Marc-Emmanuel Dumas
Jake Dunning
Tom Fletcher
Christoper A. Green
William Greenhalf
Julian L. Griffin
Rishi K. Gupta
Ewen M. Harrison
Antonia Y. W. Ho
Karl Holden
Peter W. Horby
Samreen Ijaz
Saye Khoo
Paul Klenerman
Translational Gastroenterology and Liver Unit, University of Oxford, Oxford, United Kingdom
Andrew Law
Matthew R. Lewis
Sonia Liggi
Wei Shen Lim
Lynn Maslen
Laura Merson
Alison M. Meynert
Shona C. Moore
Mahdad Noursadeghi
Michael Olanipekun
Anthonia Osagie
Massimo Palmarini
Medical Research Council-University of Glasgow Centre for Virus Research
Carlo Palmieri
William A. Paxton
Georgios Pollakis
Nicholas Price
Andrew Rambaut
David L. Robertson
Clark D. Russell
Vanessa Sancho-Shimizu
Caroline J. Sands
Janet T. Scott
Louise Sigfrid
Tom Solomon
Shiranee Sriskandan
David Stuart
Charlotte Summers
Olivia V. Swann
Zoltan Takats
Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London
Panteleimon Takis
Richard S. Tedder
A. A. Roger Thompson
Division of Clinical Medicine, University of Sheffield
Emma C. Thomson
Ryan S. Thwaites
National Heart and Lung Institute, Imperial College London
Lance CW Turtle
Maria Zambon
Thomas M. Drake
Cameron J. Fairfield
Stephen R. Knight
Kenneth A. Mclean
Derek Murphy
Lisa Norman
Riinu Pius
Catherine A. Shaw
Marie Connor
Jo Dalton
Carrol Gamble
Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, United Kingdom
Michelle Girvan
Sophie Halpin
Janet Harrison
Clare Jackson
James Lee
Laboratory of Membrane Biophysics and Biology, The Rockefeller University
Laura Marsh
Daniel Plotkin
Stephanie Roberts
Egle Saviciute
Sara Clohisey
Ross Hendry
Susan Knight
Gary Leeming
Lucy Norris
James Scott-Brown
Sarah Tait
Murray Wham
Gail Carson
Tassos Grammatikopoulos
Sarah E. McDonald
Victoria Shaw
Seán Keating
Cara Donegan
Rebecca G. Spencer
Chloe Donohue
Fiona Griffiths
Hayley Hardwick
Wilna Oosthuyzen
Timothy Rostron
Craig Waugh
Paul Sopp
Julian C. Knight
James N. Fullerton
Mark Coles
Geoffrey L. Smith
Alexander J. Mentzer
Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Yanchun Peng
Tao Dong
Department of Immunology and Microbiology, School of Life Sciences, Southern University of Science and Technology