Antibody Responses are Sustained 2 Years Post-Mpox Infection but not Following Modified Vaccinia Ankara-Bavarian...

Clade IIb mpox cases have declined globally, likely due to behavioral changes alongside vaccine- and infection-induced immunity. However, infections in vaccinated individuals raise concerns about immunity durability. We compared the longevity of antibody responses following mpox infection and modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccination.

In a multicenter, prospective cohort, we measured plasma IgG titers to vaccinia virus (VACV) B5 antigen in adults with prior mpox, MVA-BN vaccination, and historical controls, sampled up to 2 years postexposure. Receiver operating characteristic analysis determined the seropositivity threshold. Generalized additive mixed models compared antibody kinetics, and logistic regression identified factors associated with seropositivity. The results are median (interquartile range) unless specified.

A total of 122 vaccinated participants (100% male, aged 36 [32.5-43.5], 25% people with HIV [PWH]) were sampled at 22.0 (20.0-23.5) months post-MVA-BN vaccination, 72 of whom had a paired sample 12.5 (8.0-15.5) months prior, alongside 13 participants post-mpox (100% male, aged 32.5 [30.5-40], 23% PWH) sampled 25.0 (22.5-29.0) months postinfection, 12 with a paired sample 12.5 (8.5-15.5) months prior. At follow-up, 85% (11/13) of the post-mpox group remained seropositive, versus 32% (39/122) of the vaccinated group. Predicted geometric-mean anti-VACV-B5 titers fell below the seropositivity threshold at 15.5 (95% confidence interval [CI]: 13.0-19.5) months postvaccine. PWH had significantly lower odds of retaining seropositivity (odds ratio: 0.18; 95% CI: .04-.60; P = .01).

Antibody titers declined more rapidly postvaccination than post-mpox, with most vaccinated recipients, particularly PWH, losing seropositivity at 2 years. How these data relate to reinfection risk or the need for boosters remains to be determined.