NR AOPU
AU Arrighi,I.; Polymenidou,M.; Ross,T.M.; Aguzzi,A.
TI DNA vaccination strategies against prion disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-11
PT Konferenz-Poster
AB Several recent reports indicate that antibodies directed against the cellular form of the prion protein, PrPc, might eliminate the transmissible agent of spongiform encephalopathies (the prion) from scrapie-infected cells in vitro, and that a humoral immune response could prevent scrapie pathogenesis in vivo. These findings suggest that immunotherapeutical intervention against prion diseases is not unattainable. A central problem for the development of prion vaccines is to identify immunogens capable of raising high titer and long lasting antibodies that will block or delay prion propagation / replication. In order to enhance the efficacy of prion vaccines, we fused the prion protein PrPc to a component of the innate immune system, C3d. DNA constructs were produced and used for immunizations. Expression of plasmid constructs in vitro showed that these constructs were efficiently secreted from cells. Vaccine plasmids were injected intradermally. After 3 consecutive boosts, antibody titer were assessed by ELISA, FACS and western blot analysis. In prion deficient mice, C3d fused to PrPc increased the antibody titer by 1000 fold compared to other immunization procedures. However, wild type mice developed only a low antibody titer, revealing that C3d molecules might be inefficient to break tolerance for the prion protein. Immunized and control mice were inoculated with RML brain homogenate and propagation of the disease will be investigated.
AD I. Arrighi, M. Polymenidou, A. Aguzzi, Institute of Neuropathology, Zürich, Switzerland; T.M. Ross, University of Pittsburgh School of Medicine, Pittsburgh, USA
SP englisch
PO Deutschland