Immunogenicity and Reactogenicity of DTPa-HBV-IPV/Hib and PHiD-CV When Coadministered With MenACWY-TT in Infants: Results of an Open, Randomized Trial

Pediatr Infect Dis J. 2018 Jul;37(7):704-714. doi: 10.1097/INF.0000000000002061.

Abstract

Background: This study evaluated the immunogenicity and reactogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus virus-Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) and a 10-valent pneumococcal conjugate vaccine (PHiD-CV) coadministered with a quadrivalent meningococcal conjugate vaccine (MenACWY-TT) in infants/toddlers.

Methods: In this open, controlled, phase III study (NCT01144663), 2095 healthy infants were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age or MenACWY-TT, MenC-CRM197, or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immunogenicity of DTPa-HBV-IPV/Hib was evaluated in exclusive randomized subsets of 25% of participants from each group postprimary, prebooster and postbooster vaccination, whereas immunogenicity of PHiD-CV was evaluated at all time points. Reactogenicity was evaluated on the total vaccinated cohorts during 8 days after each vaccination.

Results: For each DTPa-HBV-IPV/Hib antigen, ≥97.2%, ≥76.5% and ≥97.9% of participants had seropositive/seroprotective levels 1 month postprimary vaccination, before the booster dose and 1 month postbooster, respectively. For each vaccine pneumococcal serotype, ≥74.0% of infants had antibody concentrations ≥0.35 μg/mL at 1 month postprimary vaccination, and robust increases in antibody geometric mean concentrations were observed from prebooster to postbooster. Redness was the most frequent solicited local symptom at the DTPa-HBV-IPV/Hib and PHiD-CV injection sites, reported after up to 47.7% and 57.0% of doses postprimary and postbooster vaccination, respectively.

Conclusions: Primary and booster vaccinations of infants/toddlers with DTPa-HBV-IPV/Hib and PHiD-CV coadministered with MenACWY-TT were immunogenic with clinically acceptable reactogenicity profiles. These results support the coadministration of MenACWY-TT with routine childhood vaccines.

Publication types

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

MeSH terms

  • Antibodies, Bacterial / blood*
  • Antibodies, Viral / blood
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-Pertussis Vaccine / therapeutic use*
  • Female
  • Haemophilus Vaccines / adverse effects
  • Haemophilus Vaccines / therapeutic use*
  • Hepatitis B Vaccines / adverse effects
  • Hepatitis B Vaccines / therapeutic use*
  • Humans
  • Immunization Schedule
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Infant
  • Male
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / therapeutic use
  • Poliovirus Vaccine, Inactivated / adverse effects
  • Poliovirus Vaccine, Inactivated / therapeutic use*
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / therapeutic use

Substances

  • 10-valent pneumococcal conjugate vaccine
  • Antibodies, Bacterial
  • Antibodies, Viral
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Pneumococcal Vaccines
  • Poliovirus Vaccine, Inactivated
  • Vaccines, Combined
  • diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine