title: Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.
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.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Jill B
authors.initials: JB
authors.lastname: Brelsford
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Plieskatt
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Yakovleva
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Amar
authors.initials: A
authors.lastname: Jariwala
authors.affiliation: Department of Pediatrics, Section of Pediatric Tropical Medicine, Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Keegan
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Pengjun
authors.initials: P
authors.lastname: Xia
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Doreen
authors.initials: D
authors.lastname: Campbell
authors.affiliation: Fundación Mundo Sano, Buenos Aires, Argentina.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Periago
authors.affiliation: Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.|National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.|National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Diemert
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D004355:Drug Stability; D004356:Drug Storage; D006725:Hookworm Infections / Q000517:prevention & control*; D006801:Humans; D058069:Neglected Diseases / Q000517:prevention & control*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D064166:Vaccine Potency; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D057134:Antibodies, Neutralizing; D014612:Vaccines