Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies
Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies
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DOI：
10.1126/science.1063093
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发表时间：
2001-10-05
期刊：
影响因子：
56.9
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Heppner, FL;Musahl, C;Aguzzi, A
变异克雅氏病和牛海绵状脑病是由脑外暴露于朊病毒引起的。尽管朊病毒从脑外部位传播到大脑是预防的潜在目标，但由于朊病毒蛋白的免疫原性较差，疫苗接种的尝试受到限制。为了避免这种情况，我们在Prnp（o/o）小鼠中表达了抗朊病毒蛋白（anti-PrP） mu链。转基因小鼠具有持续的抗prp滴度，且不受引入Prnp（+）等位基因的抑制。转基因表达可阻止腹腔注射引入的朊病毒在脾脏和脑内的发病。脾和脑中内源性PrP （PrPC）的表达未受影响，提示免疫起保护作用。这表明免疫抑制朊病毒疾病在体内的可行性。
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 (PrPC) 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.