title: 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, 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.
authors.affiliation: Clinical Trials Research Center, Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, Nova Scotia, Canada. scott.halperin@dal.ca
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.forename: Bruce
authors.initials: B
authors.lastname: Tapiero
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Law
authors.forename: Agnes
authors.initials: A
authors.lastname: Hoffenbach
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Zappacosta
authors.forename: David
authors.initials: D
authors.lastname: Radley
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: McCarson
authors.forename: Jason C
authors.initials: JC
authors.lastname: Martin
authors.forename: Laura E
authors.initials: LE
authors.lastname: Brackett
authors.forename: John W
authors.initials: JW
authors.lastname: Boslego
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Hesley
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Bhuyan
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Silber
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002626:Chemistry, Pharmaceutical; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine