A cohort study to evaluate persistence of hepatitis B immunogenicity after administration of hexavalent vaccines

BACKGROUND In 2001, two hexavalent vaccines were licensed in Italy (Hexavac, Infanrix Hexa), and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age). In 2005, the market authorization of Hexavac was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine. METHODS Participant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers < 10 mIU/ml, with the monovalent precursor product of the previously received hexavalent vaccine. HBsAb titers were tested again one month after the booster. RESULTS Sera from 113 children previously vaccinated with Hexavac, and from 124 vaccinated with Infanrix Hexa were tested for anti-HBs. Titers were > or = 10 mIU/ml in 69% and 96% (p < 0,0001) respectively. The proportion of children with titers > or = 100 mIU/ml did also significantly differ among groups (27% and 78%; p < 0,0001).Post-booster, 93% of children achieved titers > or = 10 mIU/ml, with no significant difference by vaccine group. DISCUSSION Fifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers < 10 mIU/ml. However, long-term persistence of HBV protection after hexavalent vaccines administration should be further evaluated over time.