NR AWME
AU Ponti,W.; Puricelli,M.; Servida,F.; Formentin,E.; Dall'Ara,P.; Poli,G.
TI Active immunization in a hamster model of scrapie
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions THE-13
PT Konferenz-Poster
AB Vaccination has been shown to be effective in mouse models for neurodegenerative conditions characterized by protein misfolding, such as Alzheimer's disease (AD) and Transmissible Spongiform Encephalopathies (TSEs). Many different immunogens and strategies of intervention have been proposed for the immunotherapy of prion diseases, based on the necessity of agent replication in lymphoid tissue prior to neuroinvasion. Here we report the use of two synthetic oligopeptides (PrP 119-146 and PrP 142-179) corresponding to the central part of hamster (Mesocricetus auratus) prion protein, as a vaccine candidate in hamster scrapie model. Immunization with these oligopeptides, in particular PrP119-146, prolonged survival time (>23 days) in animals challenged intraperitoneally with 263K strain of scrapie agent. Peptide specific seroconversion and antibody titres were measured by ELISA; brain lesions and the content of glial fibrillary acid protein (GFAP) were analysed by histopathology and immunohistochemistry. The amount of prion protein (PrPres) both in spleen and brain was evaluated by immunohistochemistry and western blotting. Moreover, mRNA expression for GFAP and pro-inflammatory cytokines (TNF-, IL-1 ) were evaluated by RT-Real Time PCR. Immunized animals showed a specific, but of low titre, antibody response. Increased survival after challenge was associated with reduction of cerebral lesions, PrP deposition (both in brain and spleen), GFAP and cytokines expression. Therefore, our results indicate that, even if associated with a modest humoral response, vaccination can slow down PrPres deposition and decrease neuroinflammation, allowing to develope a targeted strategy to prevent or reduce the pathology due to prion infections.
AD Microbiology and Immunology Unit, Department of Veterinary Pathology, Hygiene and Public Health, Faculty of Veterinary Medicine, University of Milan, Italy. E-mail: Wilma.ponti@unimi.it
SP englisch
PO Italien