Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) according to different schedules in infants in South Africa: a phase III trial

ABSTRACT

Background: Limited clinical data exists to assess differences between various infant pneumococcal conjugate vaccine schedules. In this trial, we evaluated immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) administered using 3 different immunization schedules in HIV unexposed-uninfected infants in South Africa.

Methods: In this phase III, open, single‐center, controlled study (clinicaltrials.gov: NCT00829010), 300 infants were randomized (1:1:1) to 1 of 3 PHiD-CV schedules: 3-dose priming and booster (3 + 1); 3-dose priming without booster (3 + 0); or 2-dose priming and booster (2 + 1). The booster was administered at 9–10 months of age. immune responses were assessed up to 21 months after primary vaccination.

Results: Post‐priming antibody levels tended to be lower in the 2 + 1 group. At 6 months post‐priming, antibody concentrations and opsonophagocytic activity titers were within similar ranges after 2‐ or 3‐dose priming. Robust increases were observed pre‐ to post‐booster in the 3 + 1 and 2 + 1 groups.

Conclusions: PHiD-CV was immunogenic when administered in different schedules. Post‐booster responses suggest effective immunological priming with both 2‐ and 3‐dose primary series and support administration of the booster dose at 9–10 months of age.

KEYWORDS:

• Expanded program on immunization
• immunogenicity
• pneumococcal conjugate vaccine
• safety
• vaccination schedule
• infants

Acknowledgments

The authors wish to thank investigator Dr Peter Adrian and the clinical and serological laboratory teams of the GSK group of companies for their contribution to this study, in particular Sudheer Ravula (GSK) for statistical analysis, Mireille Venken (GSK), Janice Beck, Kristel Vercauteren, Domenica Majorino (XPE Pharma & Science c/o GSK) and Ann Dhoest (freelance for GSK) for protocol and clinical report writing; Charlotte de Buck van Overstraeten, Catena Lauria (GSK) and Katleen Van Hoefs (Keyrus Biopharma c/o GSK) for global study management. The authors also thank Joke Vandewalle (XPE Pharma & Science c/o GSK) for drafting the manuscript; and Stéphanie Deroo (XPE Pharma & Science c/o GSK) for manuscript coordination.

Declaration of interest

S.A Madhi received grants from GSK, Pfizer, Novartis and Sanofi for the conduct of clinical trials and consulting fees for advisory boards and/or speaker’s bureaus from GSK, Pfizer and Sanofi. M Moreira is an employee of the GSK group of companies, owns shares of the GSK group of companies. N François is an employee of the GSK group of companies. J Ruiz-Guiñazu is an employee of the GSK group of companies, owns shares of the GSK group of companies. J.P Yarzabal is an employee of the GSK group of companies, owns shares of the GSK group of companies. D Borys is an employee of the GSK group of companies, owns shares of the GSK group of companies. L Schuerman is an employee of the GSK group of companies, owns shares of the GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Trademarks

Synflorix, Tritanrix-HepB/Hib, and Rotarix are trademarks of the GSK group of companies.

Additional information

Funding

This work was supported by GlaxoSmithKline Biologicals SA. GlaxoSmithKline Biologicals SA was involved in all stages of the study conduct and analysis. GlaxoSmithKline Biologicals SA also took responsibility for all costs associated with the development and publishing of the present manuscript.