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Publication type: Journal Article
Document type: Full Paper

Year: 2003

Author(s): Gilch, S; Wopfner, F; Renner-Müller, I; Kremmer, E; Bauer, C; Wolf, E; Brem, G; Groschup, MH; Schätzl, HM

Title: Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells.

Source: J Biol Chem. 2003; 278(20):18524-18531



Authors Vetmeduni Vienna:

Brem Gottfried

Vetmed Research Units
Institute of Animal Breeding and Genetics


Abstract:
Prion diseases are neurodegenerative infectious disorders for which no prophylactic regimens are known. In order to induce antibodies/auto-antibodies directed against surface-located PrP(c), we used a covalently linked dimer of mouse prion protein expressed recombinantly in Escherichia coli. Employing dimeric PrP as an immunogen we were able to effectively overcome autotolerance 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 endogenous PrP(Sc) synthesis. We show that polyclonal antibodies are binding to surface-located PrP(c), thereby interfering with prion biogenesis. This effect is much more pronounced in the presence of full IgG molecules, which, unlike Fab fragments, seem to induce a significant cross-linking of surface PrP. 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 PrP(Sc) conversion process. Our data point to the possibility of developing means for an active immunoprophylaxis against prion diseases.

Keywords Pubmed: Animals
Cells, Cultured
Dimerization
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Epitopes
Escherichia coli/metabolism
Female
Immunoblotting
Immunoglobulin G/chemistry
Immunoglobulin G/metabolism
Mice
Mice, Inbred C57BL
Precipitin Tests
Prions/chemistry
Prions/immunology*
Prions/metabolism
Protein Binding
Rabbits
Recombinant Proteins/chemistry
Recombinant Proteins/metabolism


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