Document Type
Journal Article
Publication Date
2-13-2017
Journal
PLoS Neglected Tropical Diseases
Volume
11
Issue
2
DOI
10.1371/journal.pntd.0005385
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Brelsford, J. B., Plieskatt, J., Yakovleva, A., Jariwala, A., Keegan, B., Peng, J., Xia, P., Li, G., Campbell, D., Periago, M., Correa-Oliveira, R., Bottazzi, M., Hotez, P. J., Diemert, D., & Bethony, J. M. (2017). Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.. PLoS Neglected Tropical Diseases, 11 (2). http://dx.doi.org/10.1371/journal.pntd.0005385
Peer Reviewed
1
Open Access
1
Included in
Medical Immunology Commons, Medical Microbiology Commons, Parasitic Diseases Commons, Parasitology Commons, Tropical Medicine Commons
Comments
Reproduced with permission of PLoS Neglected Tropical Diseases.
This version is an uncorrected proof. The final copyedited version will be available shortly.