Mpox-specific cellular and humoral immunity in mpox survivors living with HIV

The 2022 mpox virus (MPXV) outbreak caused life-threatening mpox disease in people living with HIV (PLWH). We compared immune responses to MPXV in PLWH who were either mpox-naive or were mpox survivors. We characterized the magnitude, polyfunctionality, and cytolytic potential of CD4 and CD8 T cells specific to MPXV and cross-reactive orthopoxviral antigens and compared them to HIV- and cytomegalovirus (CMV)-specific T cells. Mpox survivors developed MPXV-specific CD4 T cells capable of producing IFNγ, TNFα, and IL-2. Their polyfunctionality was superior to CMV-specific CD4 T cells. MPXV- and CMV-specific CD8 T cells had similar cytolytic potentials. Importantly, mpox survivors developed strong MPXV-specific antibodies with neutralizing activity. Prior vaccinia or JYNNEOS vaccination was associated with greater MPXV-specific antibody but not T cells. These data demonstrate that PLWH generate functional cellular and humoral immunity to MPXV post-mpox. Despite their immunocompromised state, mpox survivors with HIV are expected to have some protection against future MPXV exposures.