Immunological persistence in 4-6 and 7-9 year olds previously vaccinated in infancy with hexavalent DTPa-HBV-IPV/Hib.

BACKGROUND: The combined diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae conjugate vaccine (DTP a-HBV-IPV/Hib, Infanrix Hexa() 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 DTP a-HBV-IPV/Hib vaccine was assessed (www.clinicaltrials.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 DTP a-HBV-IPV/Hib, in previous clinical vaccine trials in Germany. RESULTS: Mean time from the fourth DTP a-HBV-IPV/Hib dose until serological follow-up ranged between 3.6 and 6.4 years. After the 4th DTP a-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 DTP a-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.

Immune memory to hepatitis B virus in 4-9-year old children vaccinated in infancy with four doses of hexavalent DTPa-HBV-IPV/Hib vaccine.

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.

Immunogenicity and reactogenicity of four doses of diphtheria-tetanus-three-component acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccine coadministered with 7-valent pneumococcal conjugate Vaccine.

BACKGROUND: The 7-valent pneumococcal (7vPn) conjugate vaccine is licensed for primary and booster vaccination according to the same immunization schedules as routinely recommended diphtheria-tetanus-pertussis-based childhood vaccines and can be coadministered during the same vaccination visit. METHODS: An open, randomized study evaluated the immunogenicity and safety of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine and a 7vPn conjugate vaccine when coadministered at 2, 3 and 4 months and 12-23 months of age, compared with the administration of the hexavalent DTPa-HBV-IPV/Hib vaccine given alone. Serum antibody titers were measured before and 1 month after the primary course and before and 1 month after the booster dose. Solicited local and general adverse events were recorded for 4 days and unsolicited adverse events were recorded for 30 days after each vaccine dose. RESULTS: A total of 345 subjects were enrolled for primary vaccination with the hexavalent vaccine (170 without and 175 with the 7vPn vaccine coadministered) and 266 returned for booster vaccination (122 without and 144 with coadministration of the 7vPn vaccine). After primary vaccination, antibody responses against the common antigens were similar in both groups, with seroprotection rates of 93.6-100% and with similar antibody decay before booster vaccination. The fourth dose induced a vigorous booster response, with seroprotection/vaccine response rates of 96.8-100%. Response to the 7vPn primary and booster vaccination was within previously reported ranges. Differences in reactogenicity resulted from higher incidences of symptoms after concomitant vaccination. Rectal temperature >39.5 degrees C was observed after 1.2% of the coadministered vaccine doses during primary vaccination and after 2.8% of the booster vaccine doses. CONCLUSION: Coadministration of the DTPa-HBV-IPV/Hib and 7vPn vaccines at separate injection sites during the same vaccination visit was effective and safe.