Electrotransfer of cDNA coding for a heterologous prion protein generates autoantibodies against native murine prion protein in wild-type mice
| Autor: | Anne Wijkhuisen, Bertrand Allard, Vincent Hanoux, Fatima Dkhissi, Jean-Yves Couraud, Didier Boquet, Fabienne Priam, Coralie Alexandrenne |
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| Přispěvatelé: | Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d'Ingénierie des Anticorps pour la Santé (LIAS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité sous contrat aromatase et oestrogènes dans les gonades des mammifères, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Anticorps recombinants, anticorps pharmacologiques, immunothérapie (EA_3515), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7) |
| Rok vydání: | 2009 |
| Předmět: |
DNA
Complementary Prions animal diseases [SDV]Life Sciences [q-bio] Recombinant Fusion Proteins Genetic Vectors Heterologous Epitopes T-Lymphocyte Biology Transfection Epitope Immune tolerance Mice Immune system Th2 Cells Species Specificity Tetanus Toxin Complementary DNA Genetics Animals Humans Molecular Biology Autoantibodies Vaccines Electroporation Autoantibody Cell Biology General Medicine Virology Molecular biology nervous system diseases Mice Inbred C57BL Immunization |
| Zdroj: | DNA and Cell Biology DNA and Cell Biology, 2010, 29 (3), pp.121-131. ⟨10.1089/dna.2009.0940⟩ |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2009.0940⟩ |
| Popis: | International audience; Prion diseases (e.g., Creutzfeldt-Jakob disease in humans) are always fatal neurodegenerative disorders characterized by conversion of the ubiquitous cellular prion protein (PrP(c)) into a pathological conformer. Immunological strategies are considered as promising prophylactic or therapeutic approaches but, unfortunately, vaccination attempts until now have been very disappointing in wild-type animals because of immune tolerance to self PrP(c). Encouraging results have come from recent experiments carried out through genetic immunization (i.e., injection in mice of cDNA coding for murine prion protein [PrP]) or heterologous protein immunization (i.e., injection in mice of PrP from another species), albeit the levels of autoantibodies in wild-type animals remained generally low. Here we investigated whether combining the potential benefits of these two last approaches, namely using genetic immunization with the cDNA coding for a heterologous PrP, could more efficiently break immune tolerance. Wild-type mice were thus vaccinated with cDNA coding for human PrP(c), fused or unfused to a stimulatory T-cell epitope, using or not using electrotransfer of DNA. After three DNA injections, mice receiving electrotransferred DNA developed a strong immune response, oriented toward the humoral Th2 type, characterized not only by high IgG1 and IgG2a antibody titers against the heterologous human PrP(c), but also, as expected, by significant amounts of autoantibodies recognizing the native conformation of murine PrP(c) expressed on cell membranes as revealed by flow cytometry and immunofluorescence. These results hence open the way for investigation of the possible protective effects of anti-PrP(c) autoantibodies in infected mouse models. More generally, our results suggest that this original immunization strategy could be of value for circumventing tolerance to poorly immunogenic proteins. |
| Databáze: | OpenAIRE |
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