Safety and immunogenicity of three different formulations of a liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 4, 6 and 12-14 months of age.

The current recommended infant vaccination schedules require many injections at multiple sites, which increase stress for infants and parents and may create challenges to vaccination compliance. Therefore, combination vaccines, which reduce the number of injections at each medical visit, can be an essential method to improve compliance. The objective of this study was to assess the safety and immunogenicity of an investigational, liquid, hexavalent, pediatric vaccine at 2, 4, 6, and 12-14 months of age. In this multicenter, open-label controlled study, 756 infants were randomized in approximately equal numbers to receive 0.5mL intramuscular dose of diptheria-tetanus-pertussis-polio-Haemophilus influenzae type b+hepatitis B vaccine, or 1 of 3 double-blind investigational formulations. All formulations included a hepatitis B surface antigen (HBsAg) concentration of 10µg/0.5mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus toxoid [PRP-T, 12µg] or Neisseria meningitidis outer membrane protein complex [PRP-OPMC, 3µg or 6µg]): a minimum acceptable postdose 3 antibody response rate for each antigen was defined by the lower limit of a 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited vaccine-related injection-site reactions (pain, erythema, swelling) with increasing PRP-OMPC dose. No serious vaccine-related AEs were reported in the investigational groups. Both PRP-OMPC formulations met prespecified acceptability criteria for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and poliovirus. The PRP-T formulation met the acceptability criterion for antibody responses to all antigens other than PRP at postdose 3. Postdose 4 responses were adequate for all antigens in all formulations. All vaccine formulations were well-tolerated. Both PRP-OMPC formulations met prespecified immunogenicity criteria of PRP-OMPC evaluation.

Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age.

Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.

Safety and immunogenicity of two formulations of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae conjugate-hepatitis B vaccine in 15 to 18-month-old children.

Combination vaccines decrease the number of injections and improve parental satisfaction and vaccination schedule compliance. In a phase 1, randomized, partially-blinded, single-dose booster study, we evaluated two formulations of an investigational liquid hexavalent vaccine containing diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate and hepatitis B surface antigen (DTaP-IPV-Hib-HBV) in 60 healthy toddlers, 15 to 18 months of age, who had been primed with three doses of a licensed pentavalent diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate (DTaP-IPV//PRP-T) vaccine. The DTaP-IPV//PRP-T vaccine was used as a control in 30 subjects. The investigational formulations, which contained the same DTaP-IPV components, differed only in Hib (content and conjugate) and HBV (content) (PRP-T/HBV10 = 12 mug Hib tetanus toxoid conjugate with 10 microg HBsAg; PRP-OMPC/HBV15 = 6 microg Hib Neisseria meningitidis outer membrane protein complex with 15 microg HBsAg). Injection-site pain, redness and swelling were reported by 46.7%, 46.7%, and 20.0% of the licensed vaccine recipients, 43.3%, 43.3%, and 26.7% of PRP-T/HBV10 recipients and 70.0%, 46.7%, and 46.7% of PRP-OMPC/HBV15 recipients, respectively. Fever > or = 37.8 degrees C and irritability were reported by 0% and 16.7% of licensed vaccine recipients, 10.3% and 23.3% of PRP-T/HBV10 recipients and 30.0% and 16.7% of PRP-OMPC/HBV15 recipients, respectively. There were no apparent differences between the groups in the proportion of participants achieving predefined, threshold or seroprotective immune responses. Geometric mean antibody levels for all antigens were similar except for anti-PRP levels, which were 19.0 microg/mL in recipients of the licensed vaccine, 40.8 microg/mL in PRP-T/HBV10 recipients and 9.4 microg/mL in PRP-OMPC/HBV15 recipients. We conclude that the hexavalent formulations appear generally well tolerated and immunogenic as a booster dose in these toddlers.