This was a prospective, multi-center study examining mpox antibody responses following infection vs. vaccination as well as factors affecting antibody persistence. Investigators enrolled people who had received 2-dose MVA-BN vaccination (marketed as Jynneos in the U.S.) or PCR-confirmed Clade IIb infection. One hundred and twenty-two participants were sampled at 22.0 months post-vaccination (72 had earlier paired samples available for comparison) and 13 participants were sampled at 25.0 months after mpox infection (12 had earlier paired samples available); all participants with a history of mpox had been unvaccinated. Twenty-five percent of the vaccine group and 23% of the mpox infection group were people with HIV: all were receiving suppressive ART (VL < 50 copies/mL) and most had CD4 > 350 cells/mm³. Anti-VACV-B5 IgG titers were significantly higher in participants with a history of mpox infection (sampled at a median of 25.0 months post-infection) compared to vaccine group participants (sampled at a median of 22.0 months post-vaccination). At two years, 85% in the mpox infection group remained seropositive compared to 32% in the vaccine group. The seropositive group had fewer people with HIV compared to the seronegative group (7% vs. 33%), and people with HIV were 82% less likely to maintain seropositivity post-vaccination. Post-vaccination antibody decay modeling found a steeper rate of decline in titers among people with HIV compared to people without HIV.

These data, which were shared at CROI 2025, suggest that 4-day, on-demand dosing strategies involving a “loading” double-dose of F/TDF may offer high levels of protection for female genital tract exposures.  Although the selected model did not account for all conditions and potential variables of interest, these are highly compelling findings which warrant further clinical evaluation to confirm study observations, discern whether safety and tolerability differences might favor a particular dosing strategy, and advance our understanding of how to optimize PrEP options for cisgender women.