J Gen Virol
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Published online ahead of print on 28 October 2009 as doi:10.1099/vir.0.013417-0
Journal of General Virology 2010;91:809.

A more recent version of this article appeared on March 1, 2010 Originally published as JGV in Press, 10.1099/vir.0.013417-0 on November 18, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.013417-0
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Mouse vaccination with dendritic cells loaded with prion protein (PrP) peptides overcomes tolerance and delays scrapie

Veronique Bachy1, Clara Ballerini2, Pauline Gourdain3, Aurelie Prignon3, Saci Iken3, Nadine Antoine4, Martine Rosset3 and Claude Carnaud3,5

1 King's College London, UK;
2 University of Florence, Italy;
3 INSERM U712, Paris, France;
4 University of Liège, Belgium

5 E-mail: claude.carnaud{at}inserm.fr

Prion diseases are presumably caused by the accumulation in the brain of a pathological protein called prion protein scrapie which results from the transconformation of cellular PrP, a ubiquitous glycoprotein expressed in all mammals. Since all isoforms of PrP are perceived as self by the host immune system, a major problem in designing efficient immunoprophylaxis or immunotherapy is to overcome tolerance. The present study was aimed at seeing whether bone-marrow-derived dendritic cells loaded with peptides previously shown to be immunogenic in PrP-deficient mice, can overcome tolerance in PrP-proficient wild type mice and protect them against scrapie. Results show that peptide-loaded dendritic cells elicit in such mice both lymphokine release by T cells and antibody secretion against native cellular PrP. Repeated recalls with peptide-loaded dendritic cells reduces the attack rate of 139A scrapie inoculated i.p. and retards by 40 days disease duration. Most interestingly, survival time in individual mice appears to be correlated with the level of circulating antibody against native cellular PrP.

Received 28 May 2009; accepted 21 October 2009.




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