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

Authors

Amar R. Jariwala, Albert B. Sabin Vaccine InstituteFollow
Brian Keegan, George Washington UniversityFollow
Pavithra Raghavendra, George Washington University
Jordan L. Plieskatt, George Washington UniversityFollow
Maria Elena Bottazzi, George Washington UniversityFollow
Peter J. Hotez, George Washington UniversityFollow
Jeffrey M. Bethony, George Washington UniversityFollow

Document Type

Poster

Publication Date

5-16-2011

Keywords

Potency; Hookworm; Recombinant Vaccine; Na-GST-1

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 . 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.

Comments

Presented at: 14th Annual Conference on Vaccine Research, May 2011, Baltimore, Maryland.

Peer Reviewed

1

Open Access

1