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

Nat Commun. 2025 May 10;16(1):4362. doi: 10.1038/s41467-025-59370-5.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Movement / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunologic Memory* / immunology
  • Male
  • Memory T Cells* / immunology
  • Mpox, Monkeypox* / immunology
  • Smallpox Vaccine
  • Vaccination
  • Vaccinia virus / immunology
  • Viral Vaccines* / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Smallpox Vaccine
  • Viral Vaccines