Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2–4 years: A phase II randomized study

Abstract

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2–4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2–4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Keywords:

• pneumococcal protein
• pneumococcal vaccine
• Gambian children
• immunogenicity
• safety

Disclosure of Potential Conflicts of Interest

MAn has received non-financial support from the GSK group of companies. MAl has received grants from the Bill & Melinda Gates Foundation. MT, VV, KD and DB are employees of the GSK group of companies. VV is co-inventor of patents related to study vaccines. VV and DB have stock options/restricted shares; KD has restricted shares from the GSK group of companies. LSHTM and GSK received support from PATH for the conduct of this trial. AO, MOO, EOO, PO and AW have no conflict of interests to declare.

Acknowledgments

We thank the parents and their children who participated in this study, the Gambian government, the EPI program of Gambia, and staff of Fajikunda Health Centre for their collaboration. We thank Joan Vive Tomas and Elizabeth Stanley-Batchilly for project management, Basiru Sanyang and the clinical trials assistants for the study site coordination and the Fajikunda field team for their field work. We appreciate support from the staff of the MRC clinical laboratories. We also thank Uduak Okomo for safety monitoring, Yolanda Lewis for study coordination, Oforiwaa Gyasi-Baiden and John Attafuah for study monitoring, Liliana Manciu for drafting the protocol and study report, and Bart van Heertum for manuscript coordination.

Authors' Contributions

AO was involved in planning, data collection, site coordination of study, review of the reported study and drafting the manuscript. MOO was involved in planning, data collection, review, project oversight on site. EOO was involved in planning/design/review of the reported study, interpretation of the results. MAn was involved in planning/design/review of the reported study, analysis plan and interpretation of the results. PO was involved in center coordination and data collection. AW was involved in center coordination, data collection and quality check. BG was involved in the study design, interpretation of the results. MAl was involved in planning/design/review of the reported study and interpretation of the results, MT was involved in planning/design/review of the reported study and statistical analysis of the data, VV was involved in planning/design/review of the reported study, interpretation of the results, and project oversight, KD was involved in interpretation of the results, coordination and reporting of the study. DB was involved in planning/design/review of the reported study, analysis plan, interpretation of the results, safety (interaction/reporting to IDMC) and project oversight. All authors have provided critical input in the manuscript and have approved the final version for submission and agreed on journal selection.

Funding

The study was funded by Medical Research Council (MRC) UK, PATH, Seattle, USA and GlaxoSmithKline Biologicals SA. Synflorix is a trademark of the GSK group of companies.