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March 18, 2009PLoS ONEOpen Access

Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie

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Key result

Immunization with dendritic cells expressing human PrP significantly prolonged mean survival time from 209 days in untreated mice to 246 days in mice infected with experimental scrapie.

Population

Wild-type C57BL/6 mice, Prnp-/- mice, and Tg650 mice (overexpressing hPrP) challenged with 139A scrapie.

Comparison

Immunization with adenovirus encoding human PrP… vs Untreated mice or mice immunized with control Ad.

Design

Preclinical

Follow-up

up to 300 days

Authors

MRMartine Bruley RossetASAntoine SacquinSLSylvie Lecollinet

Discussion

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Overview

Hypothesis-generating for prion immunotherapy; leaves open translation of DC-based PrP immunization to human disease.

Structured PICO

P
Population
Wild-type C57BL/6 mice challenged with 139A scrapie brain homogenate to evaluate the efficacy of dendritic cell-mediated immunization with xenogenic PrP.
I
Intervention
Immunization with adenovirus (Ad) encoding human PrP (hPrP) via direct injection or transfer of Ad-transduced dendritic cells (DCs).
C
Comparator
Untreated mice or mice immunized with control Ad (AdTA).
O
Outcome
Survival time after 139A scrapie challenge.hard clinical

Main Result

Effect estimate: 37 days prolongation

Absolute Event Rate: 246% vs 209%

p-value: p=0.0003

Dendritic cell-mediated immunization with xenogenic PrP breaks immune tolerance and significantly prolongs survival in a mouse model of scrapie.

Limitations

  • Animal model study which may not fully translate to human prion diseases
  • Small sample sizes per experimental group
  • The exact mechanism of protection and specific neutralizing epitopes remain to be fully elucidated

Cite This Study

Rosset et al. (2009) studied Experimental Scrapie (Prion Disease). Dendritic cell-mediated immunization with xenogenic PrP (DCTg650AdTA) vs. Untreated or control adenovirus (AdTA) was evaluated on Mean survival time (days post infection) (37 days prolongation, p=0.0003). Immunization with dendritic cells expressing human PrP significantly prolonged mean survival time from 209 days in untreated mice to 246 days in mice infected with experimental scrapie.

synapsesocial.com/papers/6a93c30240aff459acebccachttps://doi.org/10.1371/journal.pone.0004917
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Vaccination with Prion Peptide-Displaying Polyomavirus-Like Particles Prolongs Incubation Time in Scrapie-Infected Mice2021 · 8 citations
  2. 2Polylactide-Coglycolide Microspheres CoEncapsulating Recombinant Tandem Prion Protein with CpG-Oligonucleotide Break Self-Tolerance to Prion Protein in Wild-Type Mice and Induce CD4 and CD8 T Cell Responses2007 · 55 citations
  3. 3Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice2012 · 27 citations
  4. 4CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils2007 · 51 citations
  5. 5Electrotransfer of cDNA Coding for a Heterologous Prion Protein Generates Autoantibodies Against Native Murine Prion Protein in Wild-Type Mice2009 · 17 citations