Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine.
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...
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ftdoajarticles:oai:doaj.org/article:368eb2c8a79f4559b81749059cff4f88 2023-05-15T15:13:39+02:00 Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. Jill B Brelsford Jordan L Plieskatt Anna Yakovleva Amar Jariwala Brian P Keegan Jin Peng Pengjun Xia Guangzhao Li Doreen Campbell Maria Victoria Periago Rodrigo Correa-Oliveira Maria Elena Bottazzi Peter J Hotez David Diemert Jeffrey M Bethony 2017-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005385 https://doaj.org/article/368eb2c8a79f4559b81749059cff4f88 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5325600?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005385 https://doaj.org/article/368eb2c8a79f4559b81749059cff4f88 PLoS Neglected Tropical Diseases, Vol 11, Iss 2, p e0005385 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005385 2022-12-31T03:41:33Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 2 e0005385 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Jill B Brelsford Jordan L Plieskatt Anna Yakovleva Amar Jariwala Brian P Keegan Jin Peng Pengjun Xia Guangzhao Li Doreen Campbell Maria Victoria Periago Rodrigo Correa-Oliveira Maria Elena Bottazzi Peter J Hotez David Diemert Jeffrey M Bethony Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Jill B Brelsford Jordan L Plieskatt Anna Yakovleva Amar Jariwala Brian P Keegan Jin Peng Pengjun Xia Guangzhao Li Doreen Campbell Maria Victoria Periago Rodrigo Correa-Oliveira Maria Elena Bottazzi Peter J Hotez David Diemert Jeffrey M Bethony |
author_facet |
Jill B Brelsford Jordan L Plieskatt Anna Yakovleva Amar Jariwala Brian P Keegan Jin Peng Pengjun Xia Guangzhao Li Doreen Campbell Maria Victoria Periago Rodrigo Correa-Oliveira Maria Elena Bottazzi Peter J Hotez David Diemert Jeffrey M Bethony |
author_sort |
Jill B Brelsford |
title |
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
title_short |
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
title_full |
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
title_fullStr |
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
title_full_unstemmed |
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine. |
title_sort |
advances in neglected tropical disease vaccines: developing relative potency and functional assays for the na-gst-1/alhydrogel hookworm vaccine. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005385 https://doaj.org/article/368eb2c8a79f4559b81749059cff4f88 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 2, p e0005385 (2017) |
op_relation |
http://europepmc.org/articles/PMC5325600?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005385 https://doaj.org/article/368eb2c8a79f4559b81749059cff4f88 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005385 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
2 |
container_start_page |
e0005385 |
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1766344179009454080 |