Antibodies to a Nonconjugated Prion Protein Peptide 95-123 Interfere with PrP Sc Propagation in Prion-Infected Cells
- 89 Downloads
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).
- Gilch, S., Winklhofer, K. F., Groschup, M. H., Nunziante, M., Lucassen, R., Spielhaupter, C., Muranyi, W., Riesner, D., Tatzelt, J., and Schatzl, H. M. (2001). Intracellular re-routing of prion protein prevents propagation of PrPSc and delays onset of prion disease. EMBO J. 20:3957–3966.PubMedCrossRefGoogle Scholar
- Gilch, S., Wopfner, F., Renner-Muller, I., Kremmer, E., Bauer, C., Wolf, E., Brem, G., Groschup, M. H., and Schatzl, H. M. (2003). Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion infected cells. J. Biol. Chem. 278:18524–18531.PubMedCrossRefGoogle Scholar
- Long, J. R., Tang, L. M., Qiu, X. P., Zeng, F. T., Xie, X. H., and Zhang, Y. P. (2004). Sequence variation in the rabbit major histocompatibility complex DQA gene. Proceedings of the 8th World Rabbit Congress, Puebla, Mexico: 96–101.Google Scholar
- Magri, G., Clerici, M., Dall’Ara, P., Biasin, M., Caramelli, M., Casalone, C., Giannino, M. L., Longhi, R., Piacentini, L., Della Bella, S., Gazzuola, P., Martino, P. A., Della Bella, S., Pollera, C., Puricelli, M., Servida, F., Crescio, I., Boasso, A., Ponti, W., and Poli, G. (2005). Decrease in pathology and progression of scrapie after immunization with synthetic prion protein peptides in hamsters. Vaccine 23:2862–2868.PubMedCrossRefGoogle Scholar
- Peretz, D., Williamson, R. A., Kaneko, K., Vergara, J., Leclerc, E., Schmitt-Ulms, G., Mehlhorn, I. R., Legname, G., Wormald, M. R., Rudd, P. M., Dwek, R. A., Burton, D. R., and Prusiner, S. B. (2001). Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412:739–743.PubMedCrossRefGoogle Scholar
- Polymenidou, M., Heppner, F. L., Pellicioli, E. C., Urich, E., Miele, G., Braun, N., Wopfner, F., Schatzl, H. M., Becher, B., and Aguzzi, A. (2004). Humoral immune response to native eukaryotic prion protein correlates with anti-prion protection. Proc. Natl. Acad. Sci. USA 101:14670–14676.PubMedCrossRefGoogle Scholar
- Tagliavini, F., Prelli, F., Verga, L., Giaccone, G., Sarma, R., Gorevic, P., Ghetti, B., Passerini, F., Ghibaudi, E., and Forloni, G. (1993). Synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro. Proc. Natl. Acad. Sci. 90(20):9678–9682.PubMedCrossRefGoogle Scholar
- Udenfriend, S., and Meienhoferm, J. (1987). The peptides: Analysis, synthesis and biology, vol. 9, Academic Press, London.Google Scholar