Increased neonatal vaccine dose or booster immunization prevents hepatitis B vaccine breakthrough infection in children from HBsAg and HBeAg positive mothers

Infants born to HBsAg/HBeAg-positive mothers remain risk for hepatitis B virus vaccine breakthrough infection (VBI). In this multicenter prospective cohort study, we assessed whether increased neonatal vaccine dose (20 μg vs. 10 μg) or booster immunization could reduce VBI among these children. Infants were vaccinated after birth and followed up to age 5. The 20 μg non-booster group sustained higher anti-HBs levels and lower seronegative rates at all follow-ups compared to the 10 μg non-booster group. Booster immunization increased antibody levels in both dose groups. By age 5, VBI incidence was highest in the 10 μg non-booster group, whereas all overt/occult infections occurred among non-booster children. Multivariate analysis suggested that both higher neonatal dose and booster immunization were associated with a reduced VBI risk, with the lowest risk observed when both strategies were combined. These findings suggest that increased neonatal vaccine dose and booster immunization may help sustain anti-HBs and reduce VBI in high-risk population.