Safety and Immunogenicity of Two Formulations of a Hexavalent Diphtheria-Tetanus-Acellular Pertussis-Inactivated Poliovirus-Haemophilus influenzae b Conjugate-Hepatitis B Vaccine in 15 to 18 Month-Old Children

Abstract

Combination vaccines decrease the number of injections and improve parental satisfaction and vaccination schedule compliance. In a phase 1, randomized, partially-blinded, single-dose booster study, we evaluated two formulations of an investigational liquid hexavalent vaccine containing diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate and hepatitis B surface antigen (DTaP-IPV-Hib-HBV) in 60 healthy toddlers, 15 to 18 months of age who had been primed with three doses of a licensed pentavalent diphtheria, tetanus, acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae b conjugate (DTaP-IPV//PRP-T) vaccine. The DTaP-IPV//PRP-T vaccine was used as a control in 30 subjects. The investigational formulations, which contained the same DTaP-IPV components, differed only in Hib (content and conjugate) and HBV (content) (PRP-T/HBV10=12 Fg Hib tetanus toxoid conjugate with 10 Fg HBsAg; PRP-OMPC/HBV15=6 Fg Hib Neisseria meningitidis outer membrane protein complex with 15 Fg HBsAg). Injection-site pain, redness, and swelling were reported by 46.7%, 46.7%, and 20.0% of the licensed vaccine recipients, 43.3%, 43.3%, and 26.7% of PRP-T/HBV10 recipients and 70.0%, 46.7%, and 46.7% of PRP-OMPC/HBV15 recipients, respectively. Fever $37.8EC and irritability were reported by 0% and 16.7% of licensed vaccine recipients, 10.3% and 23.3% of PRP-T/HBV10 recipients and 30.0% and 16.7% of PRP-OMPC/HBV15 recipients, respectively. There were no apparent differences between the groups in the proportion of participants achieving pre-defined, threshold or seroprotective immune responses. Geometric mean antibody levels for all antigens were similar except for anti-PRP levels, which were 19.0 Fg/mL in recipients of the licensed vaccine, 40.8 Fg/mL in PRP-T/HBV10 recipients, and 9.4 Fg/mL in PRP-OMPC/HBV15 recipients. We conclude that the hexavalent formulations appear generally well tolerated and immunogenic as a booster dose in these toddlers.