Potency testing for the experimental Na-GST-1 hookworm vaccine

Abstract

Over the next decade, a new generation of vaccines will target the neglected tropical diseases (NTDs). The goal of most NTD vaccines will be to reduce the morbidity and decrease the chronic debilitating nature of these often-forgotten infections – outcomes that are hard to measure in the traditional potency testing paradigm. The absence of measurable correlates of protection, a lack of permissive animal models for lethal infection, and a lack of clinical indications that do not include the induction of sterilizing immunity required us to reconsider the traditional bioassay methods for determining vaccine potency. Owing to these limitations, potency assay design for NTD vaccines will increasingly rely on a paradigm where potency testing is one among many tools to ensure that a manufacturing process yields a product of consistent quality. Herein, we discuss the evolution of our thinking regarding the design of a potency assay along these newly defined lines and its application to the release of the experimental Necator americanus-glutathione-S- transferase-1 (Na-GST-1) vaccine to prevent human hookworm infection. We discuss the necessary steps to accomplish the design and implementation of such a new potency assay as a resource for the burgeoning NTD vaccine community. Our experience is that much of the existing information is proprietary and needs to be pulled together in a single source to aid in our overall understanding of potency testing.

Keywords::

• effective dose 50
• hookworm vaccine
• neglected tropical disease vaccine
• potency assay
• probit analysis

Acknowledgements

The authors wish to acknowledge Bruce J Meade and Jane Halpern for their inspiration, advice and guidance as they came to understand how to develop a potency assay for a neglected tropical disease vaccine. They would also like to thank Pavithra Raghavendra, Kathryn Jones and Bin Zhan for their support of this project.

Financial & competing interests disclosure

This project is supported by the Sabin Vaccine Institute through funding from the Bill and Melinda Gates Foundation. 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.

No writing assistance was utilized in the production of this manuscript.