Background
People living with HIV (PLWH) comprised a large proportion of those who acquired mpox during the global outbreak. The predominant control strategy for mpox is the use of modified vaccinia virus Ankara (MVA), a smallpox vaccine. However, the efficacy and durability of this vaccine in PLWH is unclear. We investigated immune responses in PLWH with past mpox infection and those vaccinated with two doses of MVA to better understand mpox immunity in context of HIV.
Methods
Study participants were PLWH, male, virally suppressed (VL<50 c/mL) on ART with no evidence of immunosuppression (median CD4:931, IQR:394-892, CD8:515, IQR:393-892). Plasma and PBMC samples from past-infection (PI) cohort (n=9, median age= 42, IQR=36-47) and vaccination (Vax) cohort (n=8, median age =41, IQR=41-53) were taken at single time-point at least three months post-infection or post-vaccination. IgG responses to 9 mpox (MPXV) recombinant antigens (A5L, A27L, A29L, A35R, B2R, B6R, E8L, H3L, M1R) and 3 Vaccinia virus (VACV) (VA27L, VA33R, VB5R) were measured using Luminex and reported as mean fluorescent intensity (MFI). IFN-γ CD4+ and CD8+ T-cell responses were measured in response to pools of MPXV-specific and orthopoxvirus (OP)-specific peptides using ELISPOT and reported as spot forming units (SFU)/106 PBMCs.
Results
15/17 participants produced potent serological responses to MPXV and VACV antigens. No difference in serological responses was observed for 8 MPXV antigens 3 VACV antigens between PI and Vax cohorts (p=0.6). MFI for A27L (median, 95%CI), an infection-specific antigen was significantly higher (p=<0.05) in PI (2819,1754-4537) compared to Vax (133,823-1230). Notably, two PLWH in Vax cohort produced no detectable IgG to any antigens, however, both produced potent OP T-cell responses. Overall, CD4+ and CD8+ T-cell responses (median, 95%CI) to OP peptides were significantly higher (p=<0.05) in Vax cohort (46,13-200) compared to PI cohort (22,13-54) (Fig1). MPXV T-cell responses were comparable in PI and Vax cohorts (p=0.07).
Conclusions
MVA vaccination and mpox infection produced potent serological responses in PWH. MVA resulted in higher CD4+ and CD8+ T-cell responses to OP peptides in the Vax cohort which has important public health implications on how vaccines should be prioritised. These findings also highlight the importance of monitoring how these responses are sustained in PLWH. This work is relevant to an immunocompetent virally suppressed cohort with no evidence of immune activation.