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.

Abstract 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, 12 μg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3 μg or 6 μg]), and in hepatitis B surface antigen (HBsAg, 10 μg or 15 μg). 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.