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

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-specifi...

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Published in:	Cell host & microbe Vol. 31; no. 6; pp. 928 - 936.e4
Main Authors:	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., Ekström, Anna-Mia, Sette, Alessandro, Grifoni, Alba, Buggert, Marcus
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 14-06-2023 The Authors. Published by Elsevier Inc
Subjects:	CD8-Positive T-Lymphocytes Humans infectious diseases long-lived memory T cells Medicin och hälsovetenskap monkeypox mpox Mpox (monkeypox) - metabolism MPXV Poxviridae Short Smallpox - metabolism T cells Vaccinia virus VACV viral immunity MPXV VACV infectious diseases monkeypox long-lived memory T cells vaccinia virus T cells viral immunity mpox
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Summary:	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 than in controls, demonstrating enhanced functionality and skewing toward 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. [Display omitted] •Cross-reactive T cells against MPXV are found in many unexposed adults•TCF-1+ VACV-specific CD8+ T cells persist >4 decades after smallpox vaccination•MPXV-specific CD4+ and CD8+ T cells acquire functional effector phenotypes upon mpox•MPXV-specific CD8+ T cells from patients with mild mpox show high effector potential Adamo et al. demonstrate that MPXV-reactive T cells are present in many healthy blood donors—especially in older individuals. Smallpox-vaccinated individuals maintain very long-lived resting memory T cells that are cross-reactive to MPXV, whereas those recovering from mpox develop polyfunctional effector T cell responses associated with milder disease outcomes.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally Lead contact
ISSN:	1931-3128 1934-6069 1934-6069
DOI:	10.1016/j.chom.2023.04.015