NR AOXJ
AU Nitschke,C.; Flechsig,E.; Klein,M.A.; Dittmer,U.
TI Immune response in mice after immunisation against the prion protein
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-28
PT Konferenz-Poster
AB Recent studies have shown that immunisation against the prion protein (PrP) should be considered as a promising therapeutic approach for prion disease. Antibody treatment not only cures chronically prion-infected cells, but also prevents infection of susceptible cells in cell culture. Passive immunisation of mice was able to reduce prion titers in the spleen, and prevent the onset of prion disease after peripheral infection. Here we compared the efficiency of protein and DNA immunisation for induction of therapeutic levels of antibodies against the prion protein. In the first experiment, we analysed the cellular and humoral immune response in Prnpo/o mice after immunisation with recombinant murine PrP (recPrP23-231) mixed with either incomplete Freund's adjuvant (IFA) or oligodeoxynucleotide (CpG16-68). Each immunisation protocol results in activation and proliferation of PrP-specific CD4+ T cells as determined by a proliferation assay. PrP-specific antibodies were detectable by ELISA in all blood samples of each group. In a second experiment, we evaluate DNA vaccination in wild-type and Prnpo/o mice by making use of the pCG vector that contains immune-stimulatory CpG motifs and a strong viral promoter to control the expression of murine PrP (pCG-PrP). In Prnpo/o mice, we found induction of anti-PrP antibody titers similar to antibody titers obtained with a vector carrying measles virus haemagglutinin (pCG-H5). However, no anti-PrP antibody response was detectable in wild-type (C57BL/6) mice immunised with pCG-PrP either by intradermal or intramuscular injection, while immunisation with the control vector pCG-H5 provoked an antibody response. To break self-tolerance against PrP in wild-type mice, we are currently analysing an improved DNA vector carrying universally immunogenic T-helper epitopes.
AD C. Nitschke, E. Flechsig, M.A. Klein, Institute of Virology and Immunbiology, University of Würzburg, Germany; U. Dittmer, Institute of Virology, University of Essen, Germany
SP englisch
PO Deutschland