NR AOZB
AU Schulz,G.; Wopfner,F.; Gilch,S.; Maas,E.; Renner-Müller,I.; Wolf,E.; Schätzl,H.M.
TI In vivo response to anti-prion protein-immunization
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-14
PT Konferenz-Poster
AB
Prion dieases are fatal neurodegenerative encephalopathies that can be transmitted within and between humans and animals as seen with BSE and vCJD (variant Creutzfeldt-Jakob-disease) and against which no prophylactic and therapeutic regimens are known so far. We are working on an active immunization approach as prophylactic means against prion disease development to reduce the spread of these diseases.
We have previously shown that using a recombinant PrP-dimer we are able to induce an antibody response directed against PrPc in PrP-wildtype mice. We could prove that these antibodies have a strong anti-prion effect in cell culture, could characterize its underlying mechanism and identified B-cell epitopes, that are involved (Gilch et al, 2003).
Since we are confronted with the risk of inducing an autoimmune response in PrP wild type we are characterizing the T-cell response induced in mice by our immunization regimen. We have prepared total spleen homogenates of immunized and non-immunized mice and investigated the cytokine response upon (re-)stimulation with PrP-dimer antigen via FACS analysis. Using the same approach we are mapping the specific epitopes which are responsible for the T-cell response by an implemented competition assay.
Here we show that a clear Th1-specific immune response is induced by the dimeric immunogen therefore reducing the risk of autoimmune disease development. Monitoring the white blood count we did not detect elevated levels.
Our data confirm that a prophylactic immunization against prion diseases is feasible and does not result in autoimmune disease development.
AD Gunnar Schulz, Franziska Wopfner, Sabine Gilch, Elke Maas, Hermann M. Schätzl, Technical University of Munich, Institute of Virology, Germany; Ingrie Renner-Müller, Eckard Wolf, LMU Munich, Molekulare Tierzucht, Germany
SP englisch
PO Deutschland