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☆☆☆

Abstract 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 0.5 mL 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 10 μg/0.5 mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus toxoid [PRP–T, 12 μg] or Neisseria meningitidis outer membrane protein complex [PRP–OPMC, 3 μg or 6 μg]): 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.