NR AXPN
AU Kaiser-Schulz,G.; Heit,A.; Rezai,H.; Schätzl,H.M.
TI PrP with CpG in Microspheres Breaks Self-tolerance to Prion Protein and Induces CD4 and CD8 T Cell Responses
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.142
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases like CJD and BSE are fatal neurodegenerative diseases that are characterized by the conformational conversion of normal prion protein (PrPc) into the pathologic isoform PrPsc. The immune system neither shows reaction against PrPc nor PrPsc, most likely due to profound self-tolerance. We were able to partly overcome self-tolerance using recombinantly expressed dimeric PrP (tPrP). Proof of principle for anti-prion efficacy was obtained in vitro and in vivo. Here, we demonstrate the induction of a specific Th1 T cell response in wt mice immunized with tPrP and CpG. Biochemical influences like refolding conditions, ionic strength, pH and interaction with CpG affected antigenic structure and thus immunogenicity. Subcutaneous immunization with tPrP and CpG co-encapsulated in biodegradable microspheres (PLGA-MS) significantly enhanced CD4 T cell response and even more prominent the induction of CD8 T cells, since PLGA-MS function as endosomal delivery device to macrophages and dendritic cells. PLGA-MS based DNA vaccination generated only very poor humoral and T cell responses. Our data show that prophylactic and therapeutic immunization approaches against prion infections might be feasible with tPrP antigen and CpG without inducing severe side effects.
AD G. Kaiser-Schulz, H.M. Schätzl, Institute of Virology, Technical University of Munich, Germany; A. Heit, Institute of Microbiology and Immunology, Technical University of Munich, Germany; H. Rezai, Unité de Virologie et Immunologie Moléculaires, France
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: G. Kaiser-Schulz, A. Heit, H. Rezai, F. Hammerschmidt, F. Leidel, H. Wagner, M.H. Groschup und H.M. Schätzl)