Immunogenicity and safety of an investigational fully liquid hexavalent combination vaccine versus licensed combination vaccines at 6, 10, and 14 weeks of age in healthy South African infants

Pediatr Infect Dis J. 2011 Apr;30(4):e68-74. doi: 10.1097/INF.0b013e31820b93d2.

Abstract

Background: Assessment of primary vaccination of a new fully liquid, hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) in South African infants.

Methods: Infants were randomized to the following at 6, 10, and 14 weeks of age (Expanded Program on Immunization schedule): DTaP-IPV-Hep B-PRP-T (Group 1; N = 286); DTwP-Hib, hepatitis B, and OPV vaccines (Group 2; N = 286); or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth (Group 3; N = 143). Antibody titers were measured before vaccination (pertussis toxoid, filamentous hemagglutinin) and postprimary vaccination (all valences). Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates. Safety was evaluated from parental reports.

Results: Noninferiority (Group 1 minus Group 2) was demonstrated for anti-HBs, -PRP, -diphtheria, -tetanus, and -polio 1, 2, 3 (lower 95% confidence interval for the difference was -8.20 to 3.46). Anti-HBs antibody titers ≥10 mIU/mL and anti-PRP ≥0.15 μg/mL were ≥95.4% in each group. Seroprotection rates were also high for the other antigens. Seroconversion rates (4-fold increase from pre- to postvaccination) were 93.6%, 83.2%, and 95.1% in Groups 1, 2, and 3, respectively, for anti-pertussis toxoid and 93.1%, 57.7%, and 90.0% for anti-filamentous hemagglutinin. Anti-HBs GMTs were 330, 148, and 1913 mIU/mL for Groups 1, 2, and 3, respectively. Reactogenicity was similar in each group. Fever ≥39.0°C occurred in 1.7%, 0.4%, and 0.0% of infants in Groups 1, 2, and 3, respectively; no extensive limb swelling, hypotonic-hyporesponsive episodes, or vaccine-related serious adverse events were reported.

Conclusions: The new, fully liquid, investigational hexavalent vaccine in the Expanded Program on Immunization schedule, with/without hepatitis B at birth, is highly immunogenic and safe compared with control vaccines, warranting further development.

Trial registration: ClinicalTrials.gov NCT00362336.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / administration & dosage
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / adverse effects
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / 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*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Poliovirus Vaccines / administration & dosage
  • Poliovirus Vaccines / adverse effects
  • Poliovirus Vaccines / immunology*
  • South Africa
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Poliovirus Vaccines
  • Vaccines, Combined

Associated data

  • ClinicalTrials.gov/NCT00362336