Immunisation strategies against prion diseases: prime-boost immunisation with a PrP DNA vaccine containing foreign helper T-cell epitopes does not prevent mouse scrapie.
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.
Nitschke
Cindy
C
Institute of Virology and Immunobiology, University of Wuerzburg, Versbacherstr. 7, D-97078 Wuerzburg, Germany.
Flechsig
Eckhard
E
van den Brandt
Jens
J
Lindner
Nele
N
Lührs
Thorsten
T
Dittmer
Ulf
U
Klein
Michael A
MA
D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D000937:Antigen-Antibody Reactions; D015153:Blotting, Western; D005434:Flow Cytometry; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018621:PrPC Proteins / Q000276:immunology*; D018620:PrPSc Proteins / Q000276:immunology; D017096:Prion Diseases / Q000517:prevention & control*; D011328:Prions / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA