A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.
Background Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putativ...
Published in: | PLOS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:be96f1829afd483789795737d1949860 2023-06-11T04:10:01+02:00 A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. David J Diemert Rodrigo Correa-Oliveira Carlo Geraldo Fraga Frederico Talles Marcella Rezende Silva Shital M Patel Shirley Galbiati Jessie K Kennedy Jordan S Lundeen Maria Flavia Gazzinelli Guangzhao Li Lara Hoeweler Gregory A Deye Maria Elena Bottazzi Peter J Hotez Hana M El Sahly Wendy A Keitel Jeffrey Bethony Robert L Atmar 2023-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011236 https://doaj.org/article/be96f1829afd483789795737d1949860 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011236 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011236 https://doaj.org/article/be96f1829afd483789795737d1949860 PLoS Neglected Tropical Diseases, Vol 17, Iss 3, p e0011236 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011236 2023-05-07T00:31:57Z Background Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. Methods A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 μg, 30 μg, and 100 μg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. Results Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 3 e0011236 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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 David J Diemert Rodrigo Correa-Oliveira Carlo Geraldo Fraga Frederico Talles Marcella Rezende Silva Shital M Patel Shirley Galbiati Jessie K Kennedy Jordan S Lundeen Maria Flavia Gazzinelli Guangzhao Li Lara Hoeweler Gregory A Deye Maria Elena Bottazzi Peter J Hotez Hana M El Sahly Wendy A Keitel Jeffrey Bethony Robert L Atmar A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge. Methods A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 μg, 30 μg, and 100 μg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit. Results Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered ... |
format |
Article in Journal/Newspaper |
author |
David J Diemert Rodrigo Correa-Oliveira Carlo Geraldo Fraga Frederico Talles Marcella Rezende Silva Shital M Patel Shirley Galbiati Jessie K Kennedy Jordan S Lundeen Maria Flavia Gazzinelli Guangzhao Li Lara Hoeweler Gregory A Deye Maria Elena Bottazzi Peter J Hotez Hana M El Sahly Wendy A Keitel Jeffrey Bethony Robert L Atmar |
author_facet |
David J Diemert Rodrigo Correa-Oliveira Carlo Geraldo Fraga Frederico Talles Marcella Rezende Silva Shital M Patel Shirley Galbiati Jessie K Kennedy Jordan S Lundeen Maria Flavia Gazzinelli Guangzhao Li Lara Hoeweler Gregory A Deye Maria Elena Bottazzi Peter J Hotez Hana M El Sahly Wendy A Keitel Jeffrey Bethony Robert L Atmar |
author_sort |
David J Diemert |
title |
A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
title_short |
A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
title_full |
A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
title_fullStr |
A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
title_full_unstemmed |
A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area. |
title_sort |
randomized, controlled phase 1b trial of the sm-tsp-2 vaccine for intestinal schistosomiasis in healthy brazilian adults living in an endemic area. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011236 https://doaj.org/article/be96f1829afd483789795737d1949860 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 3, p e0011236 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011236 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011236 https://doaj.org/article/be96f1829afd483789795737d1949860 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011236 |
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PLOS Neglected Tropical Diseases |
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17 |
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3 |
container_start_page |
e0011236 |
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