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<p>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<sup>+</sup> and CD4<sup>+</sup> 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<sub>18-26</sub>-specific CD8<sup>+</sup> T cell response. While tetramer<sup>+</sup>CD8<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月10日

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  • 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,
  • Peter JM Openshaw,
  • Beatrice Alex,
  • Petros Andrikopoulos,
  • Benjamin Bach,
  • Wendy S. Barclay,
  • Debby Bogaert,
  • Meera Chand,
  • 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,
  • 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,
  • 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,
  • Panteleimon Takis,
  • Richard S. Tedder,
  • A. A. Roger Thompson,
  • Emma C. Thomson,
  • Ryan S. Thwaites,
  • 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,
  • Michelle Girvan,
  • Sophie Halpin,
  • Janet Harrison,
  • Clare Jackson,
  • James Lee,
  • 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,
  • Yanchun Peng,
  • Tao Dong

摘要

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.