T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination.
Chen J-L., Wang B., Lu Y., Antoun E., Bird O., Drennan PG., Yin Z., Liu G., Yao X., Pidoux M., Bates A., Jayathilaka D., Wang J., Angus B., Beer S., Espinosa A., Baillie JK., Semple MG., ISARIC4C Investigators None., Rostron T., Waugh C., Sopp P., Knight JC., Fullerton JN., Coles M., Smith GL., Mentzer AJ., Peng Y., Dong T.
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.