Parenteral immunization with killed whole cell bacteria is one of the oldest and most successful approaches to vaccine-induced protection against bacterial disease.  Whole cell vaccines have been applied to control epidemics and have considerably diminished the burden of vaccine preventable diseases over the last century.   A whole cell vaccine for protection of children from streptococcus pneumonia could solve the problems of complex manufacturing processes, high costs, adequate supply and broad serotype coverage which are all issues with the current pneumococcal conjugate vaccines. This study will be the first in a series of studies conducted in Kenya to assess whether PATH-wSP can induce immunity against pneumococcus. With a goal of developing a vaccine to be used in an infant EPI program.

This study will utilize 600-µg and 1000-µg doses of PATH-wSP to provide a consistent dose across VAC 002 and VAC-010 (ie, 600 µg) and to explore a higher dose (1000 µg) to provide added immune and safety range data in adults. The current toxicology data support clinical trials up to 1000 µg for PATH‑wSP. Given the lack of response of most immune measurements below 600 µg as well as a safety profile that did not demonstrate dose or repeat vaccination concerns, the adult dose will be increased to 1000 µg in this study to observe for an optimal dose response. Following favorable safety results in adults, toddlers will be tested at doses of 300 and 600 mg. In addition, the upper boundary of 1000 mg in adults provides a safety margin for testing the 600-µg dose in toddlers.  

The active control vaccines in toddlers (Synflorix and Pentavac) were chosen as they are the current vaccines given in the Kenyan infant vaccination program, and would be the vaccines given concomitantly when PATH-wSP is tested in the target infant population. The majority components of these 2 vaccines have been shown to induce boosting during the second year of life, and are recognized as providing additional benefit by either the WHO or included in country-specific labels for the individual components of the vaccines (WHO 2012, EMA 2011, CDC 2013). In addition, catch-up programs have shown these vaccines to be safe when given to toddlers. Currently the Kenya EPI program does not provide booster vaccinations for the second year of life. Toddlers in this trial will be receiving this health benefit of boosting antibody responses for those common childhood diseases.

Further studies in infant populations will follow and will include (in addition to safety and immunogenicity) the effect on pneumococcal NPC. Ultimately, this data package will support a vaccine efficacy study in the pediatric population at high risk for pneumococcal disease in low-resource settings with the goal of achieving national/regional regulatory approval and WHO prequalification for access in such countries.