Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox

Adamo, Sarah, Gao, Yu, Sekine, Takuya, Mily, Akhirunnesa, Wu, Jinghua, Storgärd, Elisabet, Westergren, Victor, Filén, Finn, Treutiger, Carl-Johan, Sandberg, Johan K., Sällberg, Matti, Bergman, Peter, Llewellyn-Lacey, Sian, Ljunggren, Hans-Gustaf, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Ekström, Anna-Mia, Sette, Alessandro, Grifoni, Alba and Buggert, Marcus 2023. Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox. Cell Host & Microbe 31 (6) , pp. 928-936. 10.1016/j.chom.2023.04.015

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Abstract

Mpox represents a persistent health concern with varying disease severity. Reinfections with mpox virus (MPXV) are rare, possibly indicating effective memory responses to MPXV or related poxviruses, notably vaccinia virus (VACV) from smallpox vaccination. We assessed cross-reactive and virus-specific CD4+ and CD8+ T cells in healthy individuals and mpox convalescent donors. Cross-reactive T cells were most frequently observed in healthy donors over 45 years. Notably, long-lived memory CD8+ T cells targeting conserved VACV/MPXV epitopes were identified in older individuals more than four decades after VACV exposure and exhibited stem-like characteristics, defined by T cell factor-1 (TCF-1) expression. In mpox convalescent donors, MPXV-reactive CD4+ and CD8+ T cells were more prevalent compared to controls, demonstrating enhanced functionality and skewing towards effector phenotypes, which correlated with milder disease. Collectively, we report robust effector memory MPXV-specific T cell responses in mild mpox and long-lived TCF-1+ VACV/MPXV-specific CD8+ T cells decades after smallpox vaccination.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Cell Press
ISSN:	1931-3128
Date of First Compliant Deposit:	24 May 2023
Date of Acceptance:	19 April 2023
Last Modified:	30 Jun 2023 05:52
URI:	https://orca.cardiff.ac.uk/id/eprint/159931

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