Two-year durability of MVA-BN vaccine-induced antibodies and the risk of Mpox breakthrough infections among high-risk populations: a prospective, longitudinal study.

OBJECTIVES

Since the 2022 global Mpox outbreak, vaccination programmes 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

A total of 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. In addition, 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, although 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 after two-dose MVA-BN vaccination wanes over time, particularly among individuals without prior smallpox vaccination, whereas natural Mpox infection is associated with more durable Mpox virus-specific IgG responses. Breakthrough infections may occur more than 2 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.