Potency Testing for NTD Vaccines: Determining Relative Potency for the Na-GST-1 Human Hookworm Vaccine

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 . This potency test is a bioassay using BALB/c mice, which evaluates the immunogenicity of the vaccine at set time interval post manufacture . Herein, we discuss the results of 12 month potency testing of Necator americanus-glutathione-S- transferase-1 (Na-GST-1) vaccine . The Effective Dose 50 (ED50), with its 95% fiducial limits (FL) for each time point was determined along with the Relative Potency with its 95% FL for 3, 6, 9 and 12 months post manufacture . Potency testing has shown that storage at 4° C decreases the ED50 and increases the relative potency of Na-GST-1 vaccine . We proposed that the change in ED50 and relative potency coincide with higher affinity binding of the Na-GST-1 to the Alhydrogel® that occurred during storage at 4° C . These preclinical results lay the foundation for moving forward with Phase 1 clinical trial in Brazil