A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

Abstract

As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted.

 

This study is registered at www.clinicaltrials.gov NCT number: NCT01106092

Keywords: :

• booster
• vaccine
• polio
• combination vaccines
• immunogenicity

Disclosure of Potential Conflicts of Interest

B.Q. received an honorarium from GSK Biologicals to conduct this study and has received research grants and travel grants from Sanofi, Novartis and GSK Biologicals. O.V.M., D.K. and S.G. are employees of GlaxoSmithKline Biologicals.

Acknowledgments

The authors would like to thank Petra Vandenberk for the study coordination, Vrushali Sanghrajka (GlaxoSmithKline Biologicals) for performing the statistical analysis, Geetha Subramanyam for early work on the manuscript, Dr Joanne Wolter (independent medical writer) for preparing the first draft of the manuscript, and Dr Julia Donnelly for editorial assistance.

Sources of Support

GlaxoSmithKline Biologicals (GSK) was the funding source and was involved in all stages of the study conduct and analysis. GSK also funded all costs associated with the development and the publishing of the present manuscript. The corresponding author had full access to the data and was responsible for submission of the publication.