Cargando…

Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis

Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relat...

Descripción completa

Detalles Bibliográficos
Autores principales: Nawaratna, Sujeevi S. K., Gobert, Geoffrey N., Willis, Charlene, Mulvenna, Jason, Hofmann, Andreas, McManus, Donald P., Jones, Malcolm K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607944/
https://www.ncbi.nlm.nih.gov/pubmed/26472258
http://dx.doi.org/10.1038/srep15069
_version_ 1782395577830473728
author Nawaratna, Sujeevi S. K.
Gobert, Geoffrey N.
Willis, Charlene
Mulvenna, Jason
Hofmann, Andreas
McManus, Donald P.
Jones, Malcolm K.
author_facet Nawaratna, Sujeevi S. K.
Gobert, Geoffrey N.
Willis, Charlene
Mulvenna, Jason
Hofmann, Andreas
McManus, Donald P.
Jones, Malcolm K.
author_sort Nawaratna, Sujeevi S. K.
collection PubMed
description Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16–25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.
format Online
Article
Text
id pubmed-4607944
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46079442015-10-28 Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis Nawaratna, Sujeevi S. K. Gobert, Geoffrey N. Willis, Charlene Mulvenna, Jason Hofmann, Andreas McManus, Donald P. Jones, Malcolm K. Sci Rep Article Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16–25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection. Nature Publishing Group 2015-10-16 /pmc/articles/PMC4607944/ /pubmed/26472258 http://dx.doi.org/10.1038/srep15069 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Nawaratna, Sujeevi S. K.
Gobert, Geoffrey N.
Willis, Charlene
Mulvenna, Jason
Hofmann, Andreas
McManus, Donald P.
Jones, Malcolm K.
Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title_full Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title_fullStr Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title_full_unstemmed Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title_short Lysosome-associated membrane glycoprotein (LAMP) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
title_sort lysosome-associated membrane glycoprotein (lamp) – preliminary study on a hidden antigen target for vaccination against schistosomiasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607944/
https://www.ncbi.nlm.nih.gov/pubmed/26472258
http://dx.doi.org/10.1038/srep15069
work_keys_str_mv AT nawaratnasujeevisk lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT gobertgeoffreyn lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT willischarlene lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT mulvennajason lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT hofmannandreas lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT mcmanusdonaldp lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis
AT jonesmalcolmk lysosomeassociatedmembraneglycoproteinlamppreliminarystudyonahiddenantigentargetforvaccinationagainstschistosomiasis