Document Detail


Dendritic cell-mediated-immunization with xenogenic PrP and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.
MedLine Citation:
PMID:  19295917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Martine Bruley Rosset; Antoine Sacquin; Sylvie Lecollinet; Thomas Chaigneau; Micheline Adam; François Crespeau; Marc Eloit
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-19
Journal Detail:
Title:  PloS one     Volume:  4     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2009  
Date Detail:
Created Date:  2009-03-19     Completed Date:  2009-05-14     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e4917     Citation Subset:  IM    
Affiliation:
INSERM UMR 938, Paris, France. martine.rosset@inserm.fr
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae* / genetics,  immunology
Amino Acid Sequence
Animals
Dendritic Cells / immunology*
Genetic Vectors* / genetics,  immunology
Humans
Immunization
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
Prions / genetics,  immunology*
Scrapie / immunology*,  pathology,  prevention & control
Sequence Alignment
Survival Rate
Chemical
Reg. No./Substance:
0/Prions
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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