Koller Michael F, Grau Thomas, Christen Philipp
Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
J Neuroimmunol. 2002 Nov;132(1-2):113-6. doi: 10.1016/s0165-5728(02)00316-8.
The causative and infectious agent of the transmissible spongiform encephalopathies, e.g. bovine spongiform encephalopathy in cattle or variant Creutzfeldt-Jakob disease in humans, is a pathogenic form of the scrapie prion protein (PrP(Sc)) generated by a conformational rearrangement in the normal cellular prion protein (PrP(C)). Anti-PrP antibodies have been shown to exert a protective effect against infection with PrP(Sc). However, the generation of anti-PrP antibodies has proven quite difficult in wild-type animals, PrP being a notoriously poor immunogen. We developed a vaccine against PrP by mixing recombinant murine PrP 23-231 with DnaK, an Hsp70 homolog in Escherichia coli, and cross-linking the two proteins by means of glutaraldehyde. After three injections of the vaccine into BALB/c mice at 6, 8 and 9 weeks of age, a low-titer immune response was detected with ELISA in all animals. The specificity of the antibodies for PrP was confirmed with Western blotting. The straightforward procedure might render active immunization against prion infection feasible.
可传播性海绵状脑病（例如牛的牛海绵状脑病或人类的变异型克雅氏病）的病原体和感染因子是正常细胞朊病毒蛋白（PrP(C)）通过构象重排产生的致病性瘙痒病朊病毒蛋白（PrP(Sc)）形式。抗PrP抗体已被证明对PrP(Sc)感染具有保护作用。然而，在野生型动物中，抗PrP抗体的产生已被证明相当困难，因为PrP是一种众所周知的不良免疫原。我们通过将重组鼠PrP 23-231与大肠杆菌中的Hsp70同源物DnaK混合，并通过戊二醛交联这两种蛋白质，开发了一种针对PrP的疫苗。在6、8和9周龄时向BALB/c小鼠三次注射该疫苗后，通过ELISA在所有动物中检测到低滴度免疫反应。通过蛋白质印迹法确认了抗体对PrP的特异性。这种简单的方法可能使针对朊病毒感染的主动免疫成为可行。
