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Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection

Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed b...

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Autores principales: Crosnier, Cecile, Brandt, Cordelia, Rinaldi, Gabriel, McCarthy, Catherine, Barker, Colin, Clare, Simon, Berriman, Matthew, Wright, Gavin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833992/
https://www.ncbi.nlm.nih.gov/pubmed/31728414
http://dx.doi.org/10.12688/wellcomeopenres.15487.1
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author Crosnier, Cecile
Brandt, Cordelia
Rinaldi, Gabriel
McCarthy, Catherine
Barker, Colin
Clare, Simon
Berriman, Matthew
Wright, Gavin J.
author_facet Crosnier, Cecile
Brandt, Cordelia
Rinaldi, Gabriel
McCarthy, Catherine
Barker, Colin
Clare, Simon
Berriman, Matthew
Wright, Gavin J.
author_sort Crosnier, Cecile
collection PubMed
description Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins. Methods: In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from Schistosoma mansoni. This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner. Results: Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection. Conclusions: Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model.
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spelling pubmed-68339922019-11-13 Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection Crosnier, Cecile Brandt, Cordelia Rinaldi, Gabriel McCarthy, Catherine Barker, Colin Clare, Simon Berriman, Matthew Wright, Gavin J. Wellcome Open Res Research Article Background: Schistosomiasis is a major parasitic disease affecting people living in tropical and sup-tropical areas. Transmission of the parasite has been reported in 78 countries, causing significant morbidity and around 200,000 deaths per year in endemic regions. The disease is currently managed by the mass-administration of praziquantel to populations at risk of infection; however, the reliance on a single drug raises the prospect of parasite resistance to the only treatment widely available. The development of an effective vaccine would be a more powerful method of control, but none currently exists and the identification of new immunogens that can elicit protective immune responses therefore remains a priority. Because of the complex nature of the parasite life cycle, identification of new vaccine candidates has mostly relied on the use of animal models and on a limited set of recombinant proteins. Methods: In this study, we have established an infrastructure for testing a large number of vaccine candidates in mice and used it to screen 96 cell-surface and secreted recombinant proteins from Schistosoma mansoni. This approach, using standardised immunisation and percutaneous infection protocols, allowed us to compare an extensive set of antigens in a systematic manner. Results: Although some vaccine candidates were associated with a statistically significant reduction in the number of eggs in the initial screens, these observations could not be repeated in subsequent challenges and none of the proteins studied were associated with a strongly protective effect against infection. Conclusions: Although no antigens individually induced reproducible and strongly protective effects using our vaccination regime, we have established the experimental infrastructures to facilitate large-scale systematic subunit vaccine testing for schistosomiasis in a murine infection model. F1000 Research Limited 2019-10-16 /pmc/articles/PMC6833992/ /pubmed/31728414 http://dx.doi.org/10.12688/wellcomeopenres.15487.1 Text en Copyright: © 2019 Crosnier C et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Crosnier, Cecile
Brandt, Cordelia
Rinaldi, Gabriel
McCarthy, Catherine
Barker, Colin
Clare, Simon
Berriman, Matthew
Wright, Gavin J.
Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title_full Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title_fullStr Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title_full_unstemmed Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title_short Systematic screening of 96 Schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
title_sort systematic screening of 96 schistosoma mansoni cell-surface and secreted antigens does not identify any strongly protective vaccine candidates in a mouse model of infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833992/
https://www.ncbi.nlm.nih.gov/pubmed/31728414
http://dx.doi.org/10.12688/wellcomeopenres.15487.1
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