NR AWAY
AU Alexandrenne,C.; Wijkhuisen,A.; Dkhissi,F.; Padiolleau,S.; Creminon,C.; Grassi,J.; Couraud,J.Y.; Boquet,D.
TI DNA vaccine against prion diseases: a promising approach
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-01
PT Konferenz-Poster
AB Prion diseases as Creutzfeldt-Jakob are lethal to humans and other animals and are closely associated with the conformational alterations of the ubiquitous prion protein (PrPc). Recently, immuno therapy approaches have focused on the ability of antibodies to prevent propagation of the abnormal form of prion protein (PrPsc). More precisely, it has been decribed that only antibodies recognizing native cell-surface PrPc may interfere with prion pathogenesis. In this context, we are developping a DNA vaccine approach against prion disease. Our objective is to enhance antibody titers against native PrPc compared with that obtained using classical vaccination protocols. However, protective responses in wild type mice is limited, which is believed to be a consequence of T cell tolerance to the PrPc. To overcome this problem, we have developped a strategy based on modified plasmid vectors encoding a secretory isoform of the human PrPc (hPrP1-229 without the GPI anchor) fused or not with a sequence of the tetanus toxin (829-844), an universal T helper cell epitope. These constructs were compared for their capacity to induce human PrP specific immune response in C57Bl/6 mice. Intramuscular injections of those naked DNA have triggered a specific but low immune response. One hypothesis to explain this result is that the level of human PrPc protein, induced by the way of naked DNA injection, may be too low. Very recently, biodistribution studies of naked DNA vaccines showed that the number of plasmid DNA molecules surviving to transfect cells after intramuscular injection was only a small fraction of the total DNA injected. So, to enhance in vivo cells transfection efficiency, we have compared different DNA delivery methods (in vivo electroporation, and formulation with polyethylenimine or non-ionoic block copolymers) in terms of plasmid detection, transcrit and protein expression in situ (injection site and spleen). Preliminary results indicate promising ways to develop an efficient immunization protocol against prion diseases in wild type mice.
AD C. Alexandrenne, S. Padiolleau, C. Crminon, J. Grassi, D. Boquet: Commissariat à l'Energie Atomique (CEA) Saclay. Service de Pharmacologie et d'Immunologie. Bât 136. 91191 Gif sur Yvette Cedex, France; A. Wijkhuisen, F. Dkhissi, J.Y. Couraud: Equipe CEA- Université Paris VII UFR de Biologie Tour54. 75005 Paris Cedex05, France
SP englisch
PO Italien