BackgroundFew studies have assessed long term persisting immunity against hepatitis B virus (HBV) in children vaccinated during infancy with combined vaccines containing recombinant HBV surface antigen (HBs). We assessed antibody persistence and immune memory in children 4-5 years of age, previously vaccinated with four doses of combined hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™).MethodsImmune memory was assessed in 301 children through administration of a challenge dose of monovalent HBV vaccine.ResultsAt 4-5 years of age, 85.3% of subjects had persisting anti-HBs antibody concentrations ≥ 10 mIU/mL, rising to 98.6% after the HBV challenge dose. All but 12 subjects (95.8%) achieved post-challenge anti-HBs concentrations ≥ 100 mIU/mL. The post-challenge anti-HBs GMC rose by 100-fold compared to pre-challenge concentrations. An anamnestic response to the HBV vaccine challenge was observed in 96.8% of subjects, including 17/21 (81.0%) of children with initially undetectable antibodies (<3.3 mIU/mL). All but 4 of 42 subjects (90.5%) with anti-HBs antibodies <10 mIU/mL prior to the challenge dose, achieved seroprotective levels afterwards. A 4-fold rise in antibody concentration after the challenge dose was observed in 259/264 (98.1%) of initially seropositive subjects. The magnitude of the post-challenge responses was proportional to pre-challenge anti-HBs levels. No serious adverse events were reported during the study.ConclusionThe combined DTPa-HBV-IPV/Hib vaccine induced lasting immune memory against hepatitis B. Long term protection afforded by DTPa-HBV-IPV/Hib is likely to be similar to that observed following priming with monovalent HBV vaccines.Trial registrationhttp://www.clinicaltrials.gov 106789 NCT00411697

The combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine produces similar hepatitis B responses as the HBV monovalent vaccine. Booster vaccination of immunocompetent individuals primed against hepatitis B in infancy is currently not recommended. We investigated persisting immunity to hepatitis B in 4-6 (Study A; 106745) and 7-9 (Study B; 106744) year-old children primed in infancy and boosted in the second year of life with DTPa-HBV-IPV/Hib. Immunity was assessed by measuring persisting anti-HBs antibodies and evaluating the response to a challenge dose of HBV vaccine. At 4-6 years of age 86.0% of 186 subjects had persisting anti-HBs > or =10 mIU/ml increasing to 98.4% after the challenge. At 7-9 years of age, 78.0% of 186 subjects continued to have anti-HBs antibody concentrations > or =10 mIU/ml, increasing to 98.9% after the challenge. In both studies anti-HBs antibody GMC rose >80-fold. An anamnestic response to the HBV challenge was observed in 95.7% and 98.9% of subjects in Studies A and B, respectively. In both studies, 87% of 38 subjects with initially undetectable circulating anti-HBs antibodies (>3.3 IU/ml) achieved the 10 mIU/ml threshold after challenge; > or =97.0% of subjects with detectable antibodies before the challenge at least quadrupled their concentration. Post-vaccination anti-HBs concentrations were directly related to persisting antibody concentrations and the concentrations achieved after the booster dose in the second year of life. The HBV vaccine challenge dose was well tolerated. These studies show that primary and booster vaccination with combined DTPa-HBV-IPV/Hib (Infanrix hexa) induces sustained immune memory against hepatitis B up to age 9 years.

Combination vaccines induce immunity against multiple diseases in a single injection and thus facilitate delivery of complex vaccination schedules. Use of combination vaccines increases both vaccine coverage and the timeliness of vaccination.1 Infanrix hexa TM , the combined hexavalent diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccine [DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals (GSK), Rixensart, Belgium] is the only hexavalent vaccine currently licensed for primary and booster vaccination of infants and provides simultaneous protection against six major diseases of childhood. DTPa-HBV-IPV/Hib contains ≥30 IU diphtheria toxoid, ≥40 IU tetanus toxoid, 25 μg pertussis toxin (PT), 25 μg filamentous haemagglutinin (FHA), 8 μg pertactin (PRN), 10 μg recombinant HBsAg, 40D, 8D and 32D antigen units of poliovirus types 1, 2 and 3 respectively and 10 μg Hib polyribosylribitol-phosphate (PRP) conjugated to tetanus toxoid.Background: the combined diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae conjugate vaccine (Dtpa-HBV-IpV/Hib, Infanrix Hexa tM GlaxoSmithKline Biologicals, rixensart, Belgium) is the only hexavalent vaccine currently licensed for primary and booster vaccination of infants and provides simultaneous protection against six major diseases of childhood. the persistence of the immune response in children aged 4-6 and 7-9 years of age previously vaccinated with four doses of Dtpa-HBV-IpV/Hib vaccine was assessed (www.clinical trials.gov.au 106744 NCt00356564 and 106745 NCt00335881).Methods: A blood sample was collected from 403 children, all of whom had received 3-dose primary vaccination and a booster dose in the second year of life with Dtpa-HBV-IpV/Hib, in previous clinical vaccine trials in Germany.results: Mean time from the fourth Dtpa-HBV-IpV/Hib dose until serological follow-up ranged between 3.6 and 6.4 years. After the 4 th Dtpa-HBV-IpV/Hib dose, in subjects who had not received additional booster doses, seroprotective antibody levels persisted up to 9 years of age in ≥90% of subjects for diphtheria, Hib and poliomyelitis, in 77.2% subjects for Hepatitis B and in 64.7% of subjects for tetanus. Anti-pertussis toxin antibodies remained detectable in no more than 38.2% of subjects.Conclusion: With the exception of pt, the combined Dtpa-HBV-IpV/Hib induces long lasting immune response against all vaccine antigens. Falling seropositivity against pt over time supports the recommended administration of a pertussis booster dose in 5-6 year old children in Germany.

No abstract