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

Abstract

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.

Immune memory to hepatitis B persists in children aged 7–8 years, who were vaccinated in infancy with 4 doses of hexavalent DTPa-HBV-IPV/Hib (Infanrix™ hexa) vaccine

“…In clinical trials in Germany, in which children were vaccinated with 4 doses of DTPa-HBV-IPV/Hib in infancy, between 85.3% and 91.0% had persisting anti-HBs ≥10 mIU/mL at 4-6 y of age. 12,18,19 This compares with anti-HBs ≥10 mIU/mL in 92.9% of 4-6 y old vaccinated with 4 doses of Engerix™ B. 18 An anamnestic response to the challenge dose was observed in 95.7% to 96.8% of DTPa-HBV-IPV/Hib-primed children.…”

Sero-epidemiology of hepatitis B markers in the population of Tuscany, Central Italy, 20 years after the implementation of universal vaccination

“…However, the combined vaccine induces a lasting immune memory against hepatitis B; therefore, long term protection is likely to be similar to that observed following priming with monovalent HBV vaccines. [21][22][23][24][25] At present time, routine booster doses of hepatitis B vaccine do not seem necessary to sustain immunity in children vaccinated with hexavalent vaccines.…”

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

“…10 The according to protocol (ATP) persistence cohorts included those subjects who had not received diphtheria [96.5% (95% CI 92.9; 98.6) ≥0.016 IU/mL using the Vero cell assay], Hib and all three poliomyelitis types (Fig. 2).…”