Arrighi
Fakultäten » Medizinische Fakultät » Neuropathologie, Institut für » Prof. Dr. Adriano Aguzzi » Arrighi
Completed research project
| Title / Titel | Immunotherapeutic strategies against prion diseases | ||||
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| Abstract (PDF, 14 KB) | |||||
| Summary / Zusammenfassung | Several recent reports indicate that antibodies directed against the cellular form of the prion protein, PrPC, might eliminate the transmissible agent of spongiform encephalopathies (the prion) from scrapie-infected cells in vitro, and that a humoral immune response could prevent scrapie pathogenesis in vivo. These findings suggest that immunotherapeutical intervention against prion diseases is not unattainable. A central problem for the development of prion vaccines has been to identify immunogens capable of raising high titer and long lasting antibodies that will block or delay prion propagation / replication. In order to increase the efficacy of protein and DNA vaccines expressing the prion protein, we use a component of the innate immune system,C3d. This molecule is one of the final degradation products of the third complement protein C3 and amplify B lymphocyte activation. We constructed eucaryotic plasmids containing the sequence encoding the prion protein and 3 C3d molecules. We produce the proteins in COS cells supernatant. The proteins are then concentrated and injected into mice with Alum. The DNA vectors are injected intradermaly. After 3 different boost, antibody titer is assessed by ELISA, FACS and western blot analysis. Immunized and control mice will be inoculated with RML brain homogenate and propagation of the disease will be investigated. |
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| Publications / Publikationen | Heppner, F. L., I. Arrighi, U. Kalinke and A.Aguzzi (2001). Immunity against prions? Trends Mol Med 7, 477-479.Heppner, F. L., Musahl, C., Arrighi, I., Klein, M. A., Rulicke, T., Oesch, B., Zinkernagel, R. M., Kalinke, U., and Aguzzi, A. (2001a). Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies. Science 294, 178-182.Dempsey PW., Allison M., Akkaraju S., Goodnow C., Fearon D. (1996). C3d of complement as a molecular adjuvant : bridging innate and acquired immunity. Science 271, 348-350. | ||||
| Keywords / Suchbegriffe | prion disease, antibodies, immunization, therapy. | ||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Others EMBO |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 2001 to Dec 2004 |