Abstract
A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2–8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.
Highlights
Over the decade, a new generation of vaccines for the neglected tropical diseases (NTDs), especially those for helminthic parasites such schistosomiasis and hookworm (Necator americanus) will advance into clinical trials [1]
As vaccines targeting NTDs advance into clinical trials, product development and vaccine maintenance become critical activities for the success of these vaccines
We describe the development of a relative potency testing program for an NTD vaccine during five years of storage at 2–8 ̊C
Summary
A new generation of vaccines for the neglected tropical diseases (NTDs), especially those for helminthic parasites such schistosomiasis and hookworm (Necator americanus) will advance into clinical trials [1]. As with other experimental vaccines for tropical diseases, including recombinant vaccines for Plasmodium falciparum malaria [2, 3], the Na-GST-1/Alhydrogel Human Hookworm Vaccine was not developed using the conventional methods of attenuation or inactivation of the pathogen that induce sterilizing immunity in the host [1]. We describe assessing the potency of the Na-GST-1/Alhydrogel Hookworm Vaccine formulation immediately after its manufacture (“potency at lot release”) and its stability during 60 months of storage at 2–8 ̊C (“relative potency”). This vaccine potency assay program can serve as a model for the expanding NTD vaccine community and aid in the product and clinical development of the generation of recombinant NTD vaccines
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