Two-year durability of MVA-BN vaccine-induced antibodies and the risk of Mpox breakthrough infections among high-risk populations: a prospective, longitudinal study.
Abstract
Objectives
Since the 2022 global Mpox outbreak, vaccination programs using the MVA-BN vaccines have been widely implemented. However, the durability of vaccine-induced immunity remains incompletely understood.
Methods
Men who have sex with men aged ≥18 years who completed two-dose MVA-BN vaccination were enrolled in a prospective vaccination cohort. Participants with PCR-confirmed Mpox were enrolled as a comparison cohort. Anti-A29 and anti-H3 IgG were determined serially up for 24 months after vaccination or Mpox diagnosis. The primary outcome was the proportion of participants remaining seropositive for the two antibodies at 2 years. Secondary outcomes included antibody kinetics, breakthrough infection, and serological evidence suggesting asymptomatic infection.
Results
Total 452 participants were enrolled, including 425 in the vaccination cohort and 27 in the Mpox cohort. At 2 years after vaccination, anti-A29/anti-H3 IgG seropositivity was 19.5%/12.6% among people with HIV, 18.4%/9.2% among people without HIV, and 48.9%/51.1% among participants with prior smallpox vaccination. Additionally, among participants with natural Mpox infection, 2-year seropositivity for anti-A29 and anti-H3 IgG was 18.2% and 72.7%, respectively. Prior smallpox vaccination and natural Mpox infection were independently associated with a lower risk of seroreversion. During follow-up, six breakthrough Mpox infections were identified at a median of 828 days after vaccination. Breakthrough cases generally presented with fewer extragenital lesions than unvaccinated cases, though severe disease still occurred. Twenty participants demonstrated ≥4-fold increases in both anti-A29 and anti-H3 IgG without compatible symptoms, suggesting asymptomatic infection.
Conclusions
Humoral immunity following two-dose MVA-BN vaccination wanes over time, particularly among individuals without prior smallpox vaccination, whereas natural Mpox infection is associated with more durable MPXV-specific IgG responses. Breakthrough infections may occur more than two years after vaccination despite generally attenuated disease. These findings highlight the need for continued surveillance, consideration of booster vaccination strategies, and further investigation into immune correlates of protection against Mpox.