Mpox-Specific Immune Responses Elicited by Vaccination or Infection in People With HIV

Abstract In the recent mpox outbreak, people with human immunodeficiency virus (PWH) were at high risk both for contracting infection and for a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PWH) or smallpox vaccination (n = 17; all PWH) in a cohort of men who have sex with men. All PWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. Eleven of 17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both 2-dose modified vaccinia Ankara (MVA) vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination-mediated cross-reactivity to other orthopox viruses, and long-lasting durability of childhood smallpox vaccination-mediated immune responses, including in PWH.