Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies

作者：Frank L. Heppner, Christine Musahl, Isabelle Arrighi, Michael A. Klein, Thomas Rülicke, Bruno Oesch, Rolf M. Zinkernagel, Ulrich Kalinke, Adriano Aguzzi · 发表于：Science · 年份：2001 · DOI：10.1126/science.1063093 · 被引用次数：350 · 研究领域：Prion Diseases and Protein Misfolding

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.