Immunisation strategies against prion diseases: Prime-boost immunisation with a PrP DNA vaccine containing foreign helper T-cell epitopes does not prevent mouse scrapie

• Published in: Veterinary microbiology Vol. 123; no. 4; pp. 367 - 376
• Main Authors: Nitschke, Cindy, Flechsig, Eckhard, van den Brandt, Jens, Lindner, Nele, Lührs, Thorsten, Dittmer, Ulf, Klein, Michael A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 31-08-2007; Elsevier Science; Elsevier
• Subjects: animal diseases; animal models; Animals; Antibodies - blood; antibody formation; Antibody Formation - immunology; Antigen-Antibody Reactions; antigens; Biological and medical sciences; Blotting, Western; cell-mediated immunity; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; disease prevention; DNA fusion vaccine; DNA fusion vaccines; epitopes; Flow Cytometry; Fundamental and applied biological sciences. Psychology; human diseases; Human viral diseases; humoral immunity; Immune Tolerance; Immunity, Cellular - immunology; Infectious diseases; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Neurology; Non conventional transmissible agents; P30; prion diseases; Prion Diseases - prevention & control; Prion protein; prions; Prions - immunology; protective effect; PrPC Proteins - immunology; PrPSc Proteins - immunology; recombinant fusion proteins; Recombinant Fusion Proteins - immunology; Specific Pathogen-Free Organisms; T-lymphocytes; tetanus; Tetanus toxin; toxins; vaccination; vaccine development; vaccines; Vaccines, DNA - immunology; Viral diseases; Viral diseases of the nervous system; Tetanus toxin; Prion protein; P30; DNA fusion vaccine; Antigenic determinant; Scrapie; Metalloendopeptidases; Helper cell; Transforming DNA; Tentoxilysin; Degenerative disease; Spongiform encephalopathy; Ungulata; Nervous system diseases; Immunization; Prion disease; Farming animal; Enzyme; Rodentia; Genetic vaccine; Protein; Cerebral disorder; Infection; Peptidases; Vertebrata; Mammalia; Mouse; Ti Plasmid; Central nervous system disease; Hydrolases; Sheep; Artiodactyla; Veterinary; Medicine
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2007.03.032

Vaccination against prion diseases constitutes a promising approach for the treatment and prevention of the disease. Passive immunisation with antibodies binding to the cellular prion protein (PrP
C) can protect against prion disease. However, immunotherapeutic strategies with active immunisation are limited due to the immune tolerance against the self-antigen. In order to develop an anti-prion vaccine, we designed a novel DNA fusion vaccine composed of mouse PrP and immune stimulatory helper T-cell epitopes of the tetanus toxin that have previously been reported to break tolerance to other self-antigens. This approach provoked a strong PrP
C-specific humoral and cellular immune response in PrP null mice, but only low antibody titres were found in vaccinated wild-type mice. Furthermore, prime-boost immunisation with the DNA vaccine and recombinant PrP protein increased antibody titres in PrP null mice, but failed to protect wild-type mice from mouse scrapie.