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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Curative properties of antibodies against prion protein: a comparative in vitro study of monovalent fragments and divalent antibodies.
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Curative properties of antibodies against prion protein: a comparative in vitro study of monovalent fragments and divalent antibodies.

机译：抗病毒蛋白抗体的治疗特性：单价片段和二价抗体的体外比较研究。

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摘要

Prion diseases, which include Creutzfeldt-Jakob disease (CJD) in humans, are a group of devastating neurodegenerative disorders for which no therapy is yet available. However, passive immunotherapy appears to be a promising therapeutic approach, given that antibodies against the cellular prion protein (PrPc) have been shown in vitro to antagonize deposition of the disease-associated prion protein (PrPSc). Nevertheless, in vivo deleterious side effects of injected anti-PrP antibodies have been reported, mainly due to their Fc fragments and divalence. In this context, we examined here the ability of five Fabs (monovalent fragments devoid of the Fc part), prepared from antibodies already characterized in the laboratory, to inhibit prion replication in infected neuronal cells. We show that all Fabs (which all retain the same apparent affinity for PrPc as their whole antibody counterpart, as measured in EIA experiments) recognize quite well membrane bound-PrP in neuronal cells (as shown by flow cytometry analysis) and inhibit PrPSc formation in infected cells in a dose-dependent manner, most of them (four out of five) exhibiting a similar efficiency as whole antibodies. From a fundamental point of view, this report indicates that the in vitro curative effect of antibodies i) is epitope independent and only related to the efficiency of recognizing the native, membrane-inserted form of neuronal PrP and ii) probably occurs by directly or indirectly masking the PrPc epitopes involved in PrPSc interaction, rather than by cross-linking membrane bound PrPc. From a practical point of view, i.e. in the context of a possible immunotherapy of prion diseases, our data promote the use of monovalent antibodies (either Fabs or engineered recombinant fragments) for further in vivo studies.
机译：包括人类克雅氏病（CJD）在内的病毒疾病是一组毁灭性神经退行性疾病，目前尚无治疗方法。但是，鉴于已经证明抗细胞病毒蛋白（PrPc）的抗体在体外拮抗疾病相关asso病毒蛋白（PrPSc）的沉积，因此被动免疫疗法似乎是一种有前途的治疗方法。然而，已经报道了注射的抗PrP抗体的体内有害副作用，这主要是由于它们的Fc片段和差异。在这种情况下，我们在这里检查了由实验室已经表征的抗体制备的五个Fab（不含Fc部分的单价片段）抑制感染的神经元细胞中病毒复制的能力。我们显示，所有Fabs（在EIA实验中测得的所有Fabs都与它们的完整抗体对应物保留了对PrPc相同的表观亲和力），可以很好地识别神经元细胞中的膜结合PrP（如流式细胞仪分析所示）并抑制PrPc的形成。感染的细胞呈剂量依赖性，大多数（五分之四）显示出与完整抗体相似的效率。从基本的观点来看，该报告表明，抗体i）的体外治疗作用是独立于表位的，并且仅与识别天然的，膜插入形式的神经元PrP和ii）的效率有关，可能直接或间接地发生掩盖参与PrPSc相互作用的PrPc表位，而不是通过与膜结合的PrPc交联来掩盖。从实用的角度，即在可能的immuno病毒疾病免疫治疗的背景下，我们的数据促进了单价抗体（Fab或工程重组片段）在进一步体内研究中的应用。

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