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Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases
Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziqu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021144/ https://www.ncbi.nlm.nih.gov/pubmed/24847355 http://dx.doi.org/10.3389/fgene.2014.00119 |
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author | El Ridi, Rashika Tallima, Hatem Dalton, John P. Donnelly, Sheila |
author_facet | El Ridi, Rashika Tallima, Hatem Dalton, John P. Donnelly, Sheila |
author_sort | El Ridi, Rashika |
collection | PubMed |
description | Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziquantel-resistant parasites are likely to emerge at some time in the future. The disease is caused by several worm species of the genus Schistosoma. These express several classes of papain-like cysteine peptidases, cathepsins B and L, in various tissues but particularly in their gastrodermis where they employ them as digestive enzymes. We have shown that sub-cutaneous injection of recombinant and functionally active Schistosoma mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant protection (up to 73%) against an experimental challenge worm infection in murine models of schistosomiasis. The immune modulating properties of this subcutaneous injection can boost protection levels (up to 83%) when combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP). Here, we discuss these data in the context of the parasite’s biology and development, and provide putative mechanism by which the native-like cysteine peptidase induce protective immune responses. |
format | Online Article Text |
id | pubmed-4021144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-40211442014-05-20 Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases El Ridi, Rashika Tallima, Hatem Dalton, John P. Donnelly, Sheila Front Genet Microbiology Each year schistosomiasis afflicts up to 600 million people in 74 tropical and sub-tropical countries, predominantly in the developing world. Yet we depend on a single drug, praziquantel, for its treatment and control. There is no vaccine available but one is urgently needed especially since praziquantel-resistant parasites are likely to emerge at some time in the future. The disease is caused by several worm species of the genus Schistosoma. These express several classes of papain-like cysteine peptidases, cathepsins B and L, in various tissues but particularly in their gastrodermis where they employ them as digestive enzymes. We have shown that sub-cutaneous injection of recombinant and functionally active Schistosoma mansoni cathepsin B1 (SmCB1), or a cathepsin L from a related parasite Fasciola hepatica (FhCL1), elicits highly significant protection (up to 73%) against an experimental challenge worm infection in murine models of schistosomiasis. The immune modulating properties of this subcutaneous injection can boost protection levels (up to 83%) when combined with other S. mansoni vaccine candidates, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) and peroxiredoxin (PRX-MAP). Here, we discuss these data in the context of the parasite’s biology and development, and provide putative mechanism by which the native-like cysteine peptidase induce protective immune responses. Frontiers Media S.A. 2014-05-08 /pmc/articles/PMC4021144/ /pubmed/24847355 http://dx.doi.org/10.3389/fgene.2014.00119 Text en Copyright © 2014 El Ridi, Tallima, Dalton and Donnelly. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology El Ridi, Rashika Tallima, Hatem Dalton, John P. Donnelly, Sheila Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title | Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title_full | Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title_fullStr | Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title_full_unstemmed | Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title_short | Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
title_sort | induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021144/ https://www.ncbi.nlm.nih.gov/pubmed/24847355 http://dx.doi.org/10.3389/fgene.2014.00119 |
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