Wisniewski T, Chabalgoity J A, Goni F
Department of Psychiatry, New York University School of Medicine, 560 First Avenue, New York, NY 10016, USA.
Rev Sci Tech. 2007 Apr;26(1):243-51.
Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformation change of the cellular form of a normal, self-protein called a prion protein (PrP(c) [C for cellular]) to a pathological and infectious conformation known as scrapie form (PrPsc [Sc for scrapie]). Currently, all prion diseases are without effective treatment and are universally fatal. The emergence of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease has highlighted the need to develop possible therapies. In Alzheimer's disease (AD), which has similarities to prion diseases, both passive and active immunisation have been shown to be highly effective at preventing disease and cognitive deficits in model animals. In a human trial of active vaccination in AD, despite indications of cognitive benefits in patients with an adequate humoral response, 6% of patients developed significant complications related to excessive cell-mediated immunity. This experience highlights that immunotherapies designed to be directed against a self-antigen have to finely balance an effective humoral immune response with potential autoimmune toxicity. Many prion diseases have the gut as a portal of infectious agent entry. This makes mucosal immunisation a potentially very attractive method to partially or completely prevent prion entry across the gut barrier and to also produce a modulated immune response that is unlikely to be associated with any toxicity. The authors' recent results using an attenuated Salmonella vaccine strain expressing the prion protein show that mucosal vaccination can partially protect against prion infection from a peripheral source, suggesting the feasibility of this approach.
朊病毒疾病是一类独特的疾病，可影响动物和人类，其潜在发病机制与一种正常自身蛋白（称为朊病毒蛋白（PrP(c) [C代表细胞型]））的细胞形式构象转变为一种病理性且具有传染性的构象（即瘙痒病形式（PrPsc [Sc代表瘙痒病]））有关。目前，所有朊病毒疾病都没有有效的治疗方法，并且普遍致命。牛海绵状脑病和变异型克雅氏病的出现凸显了开发可能治疗方法的必要性。在与朊病毒疾病有相似之处的阿尔茨海默病（AD）中，被动免疫和主动免疫在预防模型动物的疾病和认知缺陷方面均已显示出高度有效性。在一项AD主动疫苗接种的人体试验中，尽管有迹象表明体液反应充分的患者有认知益处，但6%的患者出现了与过度细胞介导免疫相关的严重并发症。这一经验凸显出，旨在针对自身抗原的免疫疗法必须在有效的体液免疫反应与潜在的自身免疫毒性之间实现精细平衡。许多朊病毒疾病以肠道作为感染源的进入门户。这使得黏膜免疫成为一种潜在非常有吸引力的方法，可部分或完全防止朊病毒穿过肠道屏障进入，并产生一种不太可能与任何毒性相关的调节性免疫反应。作者最近使用表达朊病毒蛋白的减毒沙门氏菌疫苗株所获得的结果表明，黏膜接种可部分保护机体免受外周源朊病毒感染，这表明了该方法的可行性。
