NR AOPV
AU Bach,P.; Nikles,D.; Montrasio,F.; Heppner,F.L.; Aguzzi,A.; Buchholz,C.J.; Kalinke,U.
TI Induction of prion protein-specific antibody responses using PrP-retroparticles
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-23
PT Konferenz-Poster
AB Passive immunization with antibodies directed against the cellular form of the prion protein (PrP) can protect against prion disease. However, so far active immunization with recombinant PrP failed to induce in vivo protective antibody responses. Reasoning that on the surface of virus particles the recombinant protein would be presented in an ideal way to serve as B cell antigen, for immunization we used PrP-retroparticles displaying amino acids 121 to 231 of PrP on the envelope of murine leukemia virus like particles (for details see contribution by Nikles et al.). Indeed, PrP-retroparticle preparations devoid of adjuvant were able to induce high antibody titers in PrP deficient (Prnp-/-) mice, as evidenced by ELISA and FACS methods. Already 7 days after priming of Prnp-/- mice with PrP-retroparticle preparations containing approximately 10E10 particles, high PrP-specific titers were induced. Upon boosting, PrP-specific titers were slightly enhanced and the prevalence of PrP-specific immunoglobulin of the G subclass (IgG) was further increased. The titers remained elevated for about 4 weeks and then declined slowly. In wild type mice only very low IgM titers were induced within 7 days that then rapidly declined. Currently, various immunization protocols are being analyzed involving adjuvant and different dendritic cell subsets as antigen presenting cells to induce high PrP-specific serum titers in wild type mice. In a next step the in vitro protective capacity of PrP-specific sera will be tested.
AD P. Bach, F. Montrasio, C.J. Buchholz, U. Kalinke, Patricia Bach, Paul-Ehrlich-Institut, Germany; D. Nikles, F.L. Heppner, A. Aguzzi, University Hospital of Zürich, Switzerland
SP englisch
PO Deutschland