Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.
The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) f...
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ftdoajarticles:oai:doaj.org/article:0921b6a2d4aa4d98b2d912263b2a3913 2023-05-15T15:12:34+02:00 Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. Mark S Pearson Darren A Pickering Henry J McSorley Jeffrey M Bethony Leon Tribolet Annette M Dougall Peter J Hotez Alex Loukas 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001564 https://doaj.org/article/0921b6a2d4aa4d98b2d912263b2a3913 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3302818?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001564 https://doaj.org/article/0921b6a2d4aa4d98b2d912263b2a3913 PLoS Neglected Tropical Diseases, Vol 6, Iss 3, p e1564 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001564 2022-12-31T13:05:48Z The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 3 e1564 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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 Mark S Pearson Darren A Pickering Henry J McSorley Jeffrey M Bethony Leon Tribolet Annette M Dougall Peter J Hotez Alex Loukas Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic. |
format |
Article in Journal/Newspaper |
author |
Mark S Pearson Darren A Pickering Henry J McSorley Jeffrey M Bethony Leon Tribolet Annette M Dougall Peter J Hotez Alex Loukas |
author_facet |
Mark S Pearson Darren A Pickering Henry J McSorley Jeffrey M Bethony Leon Tribolet Annette M Dougall Peter J Hotez Alex Loukas |
author_sort |
Mark S Pearson |
title |
Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
title_short |
Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
title_full |
Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
title_fullStr |
Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
title_full_unstemmed |
Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2. |
title_sort |
enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen sm-tsp-2. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001564 https://doaj.org/article/0921b6a2d4aa4d98b2d912263b2a3913 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 3, p e1564 (2012) |
op_relation |
http://europepmc.org/articles/PMC3302818?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001564 https://doaj.org/article/0921b6a2d4aa4d98b2d912263b2a3913 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001564 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
3 |
container_start_page |
e1564 |
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1766343232813268992 |