NR ATOF
AU Schulz,G.; Heit,A.; Hammerschmidt,F.; Gilch,S.; Wagner,H.; Schätzl,H.M.
TI Vaccination approaches against prion infections
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-29
PT Konferenz-Poster
AB Prion diseases are neurodegenerative infectious disorders for which no prophylactic regimens are known. In order to induce antibodies/auto-antibodies directed against surface-located PrPc, we used a covalently linked dimer of mouse prion protein expressed recombinantly in E. coli. Employing dimeric PrP as an immunogen in combination with adjuvant CpG, we were able to effectively overcome auto-tolerance against murine PrP in PrP wild-type mice without inducing obvious side effects. Treatment of prion-infected mouse cells with polyclonal anti-PrP antibodies generated in rabbit or auto-antibodies produced in mice significantly inhibited the endogenous PrPsc synthesis. In addition, we found immune responses against different epitopes when comparing antibodies induced in rabbits and PrP wild-type mice. Only in the auto-antibody situation in mice an immune reaction against a region of PrP is found that was reported to be involved in the PrPsc conversion process. Our data clearly show that we also induce a Th1-type T-cell response in this auto-immunization situation. Studies on improved antigen application and the efficacy of tolerance breakers like anti-OX40 antibody are ongoing. Our data point to the possibility of developing an active immunoprophylaxis against prion diseases.
AD G.Schulz, F.Hammerschmidt, S.Gilch, H.M.Schätzl, Institute of Virology, Technische Universität München, Germany; A.Heit, H.Wagner, Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany
SP englisch
PO Deutschland