Antibodies to a Nonconjugated Prion Protein Peptide 95-123 Interfere with PrP Sc Propagation in Prion-Infected Cells
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1. Vaccination-induced anti-prion protein antibodies are presently regarded as a promising approach toward treatment of prion diseases. Here, we investigated the ability of five peptides corresponding to three different regions of the bovine prion protein (PrP) to elicit antibodies interfering with PrPSc propagation in prion-infected cells.
2. Rabbits were immunized with free nonconjugated peptides. Obtained immune sera were tested in enzyme-linked immunosorbent assay (ELISA) and immunoblot for their binding to recombinant PrP and cell-derived pathogenic isoform (PrPSc) and normal prion protein (PrPc), respectively. Sera positive in all tests were chosen for PrPSc inhibition studies in cell culture.
3. All peptides induced anti-peptide antibodies, most of them reacting with recombinant PrP. Moreover, addition of the serum specific to peptide 95–123 led to a transient reduction of PrPSc levels in persistently prion-infected cells.
4. Thus, anti-PrP antibodies interfering with PrPSc propagation were induced with a prion protein peptide nonconjugated to a protein carrier. These results point to the potential application of the nonconjugated peptide 95–123 for the treatment of prion diseases.
KEY WORDSprion protein prion peptide nonconjugated peptide anti-peptide antibodies
We thank Elke Maas and Dr. Alexa Ertmer for their help and advice, Dr. Max Nunziante, Gunnar Schulz and Dr. Ina Vorberg for helpful discussions and ideas. Maria Oboznaya was an exchange scientist sponsored by the DAAD. This work was supported in part by the European Union (NoE NeuroPrion), the Bavarian Government (LMU5*), and by the BMBF (01KO0108).
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