Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.

In prion diseases, PrP(c), a widely expressed protein, is transformed into a pathogenic form called PrP(Sc), which is in itself infectious. Antibodies directed against PrP(c) have been shown to inhibit PrP(c) to PrP(Sc) conversion in vitro and protect in vivo from disease. Other effectors with poten...

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Autores principales:	Martine Bruley Rosset, Antoine Sacquin, Sylvie Lecollinet, Thomas Chaigneau, Micheline Adam, François Crespeau, Marc Eloit
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97835024fb9049be8538e9f5355fb1c2
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spelling	oai:doaj.org-article:97835024fb9049be8538e9f5355fb1c22021-11-25T06:16:36ZDendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.1932-620310.1371/journal.pone.0004917https://doaj.org/article/97835024fb9049be8538e9f5355fb1c22009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19295917/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In prion diseases, PrP(c), a widely expressed protein, is transformed into a pathogenic form called PrP(Sc), which is in itself infectious. Antibodies directed against PrP(c) have been shown to inhibit PrP(c) to PrP(Sc) conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrP(c) makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs). Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrP(c). Frequencies of PrP-specific IFNgamma-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3(+) T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrP(Sc) replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses.Martine Bruley RossetAntoine SacquinSylvie LecollinetThomas ChaigneauMicheline AdamFrançois CrespeauMarc EloitPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4917 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Martine Bruley Rosset Antoine Sacquin Sylvie Lecollinet Thomas Chaigneau Micheline Adam François Crespeau Marc Eloit Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
description	In prion diseases, PrP(c), a widely expressed protein, is transformed into a pathogenic form called PrP(Sc), which is in itself infectious. Antibodies directed against PrP(c) have been shown to inhibit PrP(c) to PrP(Sc) conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrP(c) makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs). Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrP(c). Frequencies of PrP-specific IFNgamma-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3(+) T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrP(Sc) replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses.
format	article
author	Martine Bruley Rosset Antoine Sacquin Sylvie Lecollinet Thomas Chaigneau Micheline Adam François Crespeau Marc Eloit
author_facet	Martine Bruley Rosset Antoine Sacquin Sylvie Lecollinet Thomas Chaigneau Micheline Adam François Crespeau Marc Eloit
author_sort	Martine Bruley Rosset
title	Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
title_short	Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
title_full	Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
title_fullStr	Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
title_full_unstemmed	Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
title_sort	dendritic cell-mediated-immunization with xenogenic prp and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/97835024fb9049be8538e9f5355fb1c2
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Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.

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