Background
Clade IIb mpox cases have declined globally, likely due to vaccine and post-infection immunity alongside behavioural changes. However, breakthrough infections in vaccinated individuals and reports of reinfections raise questions about immune durability and the need for vaccine booster doses. We aimed to assess the durability of antibody responses following mpox and Modified Vaccinia Ankara (MVA) vaccination.
Methods
In a prospective cohort study, we measured plasma IgG titres to Vaccinia virus (VACV) B5 antigen in adults with prior mpox infection, MVA vaccination and historical controls. We used ROC analysis to define the optimum threshold for seropositivity against previously identified true positive and negative samples. Antibody kinetics post-infection or vaccination were analysed with generalised additive mixed models (GAMMs). Multivariable logistic regression identified factors associated with retaining seropositivity post-vaccination. Results are median (IQR) unless specified.
Results
A total of 122 participants (100% male, age 36 [33–44] years, 93% Caucasian, 25% people with HIV [PWH], 11% with prior smallpox vaccination) were sampled at 652 (607–700) days post MVA vaccination (72 with a paired sample 378 [237–465] days prior), alongside 13 participants (100% male, aged 33 [31–40] years, 100% Caucasian, 23% PWH, 0% with prior smallpox vaccination) at 747 (677–865) days post mpox (12 with a paired sample 378 [248– 459] prior). Anti-VACVB5 IgG titres >3284 arbitrary units/ml offered 98% (95% CI: 90–100%) sensitivity and 84% (78–95%) specificity to distinguish seropositivity. Of those with prior mpox, 85% (11/13) remained seropositive at 747 (677–865) days (figure). In contrast, the mean predicted VACVB5 titres following MVA vaccination fell below the seropositive threshold at 472 (95% CI: 389–587) days (figure), with only 32% (39/122) remaining seropositive at 652 (607–700) days. PWH had significantly lower odds of retaining seropositivity post-vaccination (OR: 0.17 [95% CI: 0.04–0.54], p=0.01), an association that persisted when adjusted for time since vaccination, age and prior smallpox vaccination, (aOR: 0.19 [95% CI: 0.04–0.61], p=0.01).
Conclusions
Post vaccination mpox VACVB5 titres declined significantly over time, with the majority, particularly PWH, losing seropositivity two years post primary vaccination while seropositivity following mpox infection persisted. How these data relate to risk of reinfection or need for booster vaccination remains to be determined.