Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies.
Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) mu chain in Prnp(o/o) mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of Prnp+ alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrP(C)) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo.
Heppner
F L
FL
Institute of Neuropathology, Institute of Laboratory Animal Science, Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
Musahl
C
C
Arrighi
I
I
Klein
M A
MA
Rülicke
T
T
Oesch
B
B
Zinkernagel
R M
RM
Kalinke
U
U
Aguzzi
A
A
D000682:Amyloid / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D001923:Brain Chemistry; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000235:genetics; D018620:PrPSc Proteins / Q000032:analysis / Q000276:immunology*; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics; D012608:Scrapie / Q000517:prevention & control*; D013154:Spleen / Q000737:chemistry / Q000276:immunology
D000682:Amyloid; D000906:Antibodies; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D018621:PrPC Proteins; D018620:PrPSc Proteins; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors