Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

Hum Vaccin Immunother. 2017 Jul 3;13(7):1505-1515. doi: 10.1080/21645515.2017.1294294. Epub 2017 Mar 24.

Abstract

Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.

Keywords: DTPa-HBV-IPV/Hib; Haemophilus influenzae type b; acellular pertussis; diphtheria; hepatitis B; immunogenicity; infants; poliovirus; safety; tetanus.

Publication types

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

MeSH terms

  • Antibodies, Bacterial / blood*
  • Antibodies, Viral / blood*
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects*
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Fever / chemically induced*
  • Fever / epidemiology
  • 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
  • Immunization Schedule
  • Infant
  • Male
  • 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
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Poliovirus Vaccine, Inactivated
  • Vaccines, Combined
  • diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Associated data

  • ClinicalTrials.gov/NCT01453998
  • ClinicalTrials.gov/NCT01248884