Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine

dc.creatorBrelsford, Jill B.
dc.creatorPlieskatt, Jordan L.
dc.creatorYakovleva, Anna
dc.creatorJariwala, Amar
dc.creatorKeegan, Brian P.
dc.creatorPeng, Jin
dc.creatorXia, Pengjun
dc.creatorLi, Guangzhao
dc.creatorCampbell, Doreen
dc.creatorPeriago, Maria Victoria
dc.creatorOliveira, Rodrigo Correa de
dc.creatorBottazzi, Maria Elena
dc.creatorHotez, Peter J.
dc.creatorDiemert, David
dc.creatorBethony, Jeffrey Michael
dc.date2018-06-05T16:50:08Z
dc.date2018-06-05T16:50:08Z
dc.date2017
dc.date.accessioned2023-09-26T20:42:28Z
dc.date.available2023-09-26T20:42:28Z
dc.identifierBRELSFORD, Jill B et al. Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. PLoS Neglected Tropical Diseases, v. 11, n. 2, p. 1-19, 2017.
dc.identifier1935-2727
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/26733
dc.identifier10.1371/journal.pntd.0005385
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8862401
dc.descriptionA 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
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectVacinas
dc.subjectDesenvolvimento de vacinas
dc.subjectVaccines
dc.subjectVaccine development
dc.subjectHookworms
dc.subjectAntibodies
dc.subjectBlood plasma
dc.subjectNeglected tropical diseases
dc.subjectRecombinant vaccines
dc.subjectDesorption
dc.titleAdvances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine
dc.typeArticle


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