Challenge with a hepatitis B vaccine in two cohorts of 4–7-year-old children primed with hexavalent vaccines : An open-label, randomised trial in Italy

Background and aims: The anamnestic response to a challenge dose of vaccine can assess immune memory and protection against hepatitis B infection. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children immunised with three doses of either Hexavac or Infanrix-Hexa during infancy. Methods: This open-label, randomised, controlled, four-arm study enrolled 410 healthy children aged 4-7 years who had received either Hexavac (n= 201) or Infanrix-Hexa (n= 209) at 3, 5 and 11 months of life. Children received a single intramuscular challenge dose of either hepatitis B vaccine, HBVaxPro (Hexavac, n= 34; Infanrix-Hexa, n= 28) or Engerix-B (Hexavac, n= 167; Infanrix-Hexa, n= 181). Hepatitis B surface antibody (anti-HBs) concentrations were measured before and 1 month after the challenge vaccine dose. The analysis was descriptive and no formal hypothesis was tested. Results: One month post-challenge, 91.2% of children in the Hexavac group (95% confidence interval [CI] 86.3, 94.8) and 98.0% (95% CI 94.9, 99.4) in the Infanrix-Hexa group had anti-HBs concentrations ≥10. mIU/ml (primary endpoint). In a post hoc analysis, most children with pre-challenge anti-HBs concentration <10. mIU/ml achieved anti-HBs concentrations ≥10. mIU/ml (Hexavac group, 85.3% [95% CI 77.6, 91.2]; Infanrix-Hexa group, 91.9% [95% CI 78.1, 98.3]). Both challenge vaccines were well tolerated. Conclusions: These data suggest that immune memory persists for long-term (5 years) after a primary vaccination in infancy with a hexavalent vaccine (Hexavac or Infanrix-Hexa).