Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity

Vaccine. 2018 Feb 8;36(7):986-996. doi: 10.1016/j.vaccine.2018.01.005. Epub 2018 Jan 12.


Background: Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.

Methods: Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.

Results: At least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens.

Conclusion: GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.

Keywords: DTPa-HBV-IPV/Hib; Hexavalent vaccine; Premature; Preterm; Primary vaccination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Global Health
  • 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
  • Immunity, Cellular
  • Immunogenicity, Vaccine
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Morbidity
  • Mortality
  • Outcome Assessment, Health Care
  • Poliovirus Vaccine, Inactivated / administration & dosage
  • Poliovirus Vaccine, Inactivated / adverse effects
  • Poliovirus Vaccine, Inactivated / immunology*
  • Product Surveillance, Postmarketing*
  • Public Health Surveillance*
  • Vaccination*
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology*


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