Safety and immunogenicity of a hexavalent vaccine administered at 2, 4 and 6 months of age with or without a heptavalent pneumococcal conjugate vaccine: a randomized, open-label study

Pediatr Infect Dis J. 2013 Jan;32(1):54-61. doi: 10.1097/INF.0b013e3182717edf.

Abstract

Background: DTaP₅-IPV-Hib-HepB, an investigational hexavalent combination vaccine, was evaluated for safety and immunogenicity, when administered to infants with heptavalent pneumococcal conjugate vaccine (PCV7).

Methods: Infants were randomized to receive DTaP₅-IPV-Hib-HepB plus PCV7, DTaP₅-IPV-Hib-HepB with PCV7 administered 1 month later or DTaP₅-IPV/Hib plus HepB plus PCV7 at 2, 4 and 6 months of age in an open-label, phase IIb trial. Vaccine responses were assessed by pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2/3 seroconversion rates, Haemophilus influenzae type b polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3 seroprotection rates and geometric mean titers. Solicited injection site and systemic reactions, serious adverse events, and other safety outcomes were reported.

Results: Seroprotection rates to polyribosylribitol phosphate, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens across all groups met or exceeded predetermined acceptability criteria. Seroconversion rates to pertussis toxoid, pertactin and fimbriae types 2/3, but not filamentous hemagglutinin, met such criteria. Antidiphtheria antibodies were significantly lower when PCV7 was coadministered. Geometric mean titers to the other antigens of the hexavalent and PCV7 vaccines were all high and similar in the 2 groups. No safety signals were noted.

Conclusions: DTaP₅-IPV-Hib-HepB administered at 2, 4 and 6 months of age concomitantly with PCV7 was well tolerated and elicited robust antibody responses to all but the antidiphtheria antigens for which there may be evidence of immune interference. Only filamentous hemagglutinin did not meet seroconversion rate acceptability criteria.

Trial registration: ClinicalTrials.gov NCT00362427.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Bacterial / immunology
  • Antigens, Viral / immunology
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage*
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology
  • Female
  • Haemophilus Vaccines / administration & dosage*
  • Haemophilus Vaccines / adverse effects*
  • Haemophilus Vaccines / immunology
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / adverse effects*
  • Hepatitis B Vaccines / immunology
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / adverse effects*
  • Pneumococcal Vaccines / immunology
  • Poliovirus Vaccine, Inactivated / administration & dosage*
  • Poliovirus Vaccine, Inactivated / adverse effects*
  • Poliovirus Vaccine, Inactivated / immunology
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Antigens, Bacterial
  • Antigens, Viral
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Pneumococcal Vaccines
  • Poliovirus Vaccine, Inactivated
  • Vaccines, Combined
  • diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Associated data

  • ClinicalTrials.gov/NCT00362427