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一种对恶性疟原虫和伯氏疟原虫环子孢子蛋白具有双重特异性的保护性单克隆抗体。

A protective monoclonal antibody with dual specificity for Plasmodium falciparum and Plasmodium berghei circumsporozoite proteins.

作者信息

Sina B J, Wright C, Ballou R, Hollingdale M

机构信息

Biomedical Research Institute, Rockville, Maryland 20852.

出版信息

Exp Parasitol. 1992 Jun;74(4):431-40. doi: 10.1016/0014-4894(92)90205-o.

DOI:10.1016/0014-4894(92)90205-o
PMID:1375561
Abstract

An IgM monoclonal antibody (Mab 36) which reacts with the circumsporozoite (CS) proteins of both P. falciparum and P. berghei was isolated from Plasmodium falciparum sporozoite-immunized mice. In assays of biological activity, Mab 36 induces the CS precipitation reaction with live sporozoites and blocks the invasion of hepatoma cells by sporozoites in vitro at concentrations much lower than those observed for previously reported CS protein-specific monoclonal antibodies. Mab 36 also provided complete protection against P. berghei sporozoite challenge in mice at low doses. Linear epitope mapping revealed that the epitope specificities recognized by Mab 36 are completely encompassed by other monoclonals previously shown to be associated in vivo with protection against P. falciparum or P. berghei sporozoite infection. These results suggest that the ability to make high-affinity IgM antibody to specific CS protein repeat epitopes may be important for eliciting protection against malarial infection.

摘要

从经恶性疟原虫子孢子免疫的小鼠中分离出一种IgM单克隆抗体(Mab 36),它可与恶性疟原虫和伯氏疟原虫的环子孢子(CS)蛋白发生反应。在生物活性检测中,Mab 36可诱导与活子孢子的CS沉淀反应,并在体外以远低于先前报道的CS蛋白特异性单克隆抗体的浓度阻断子孢子对肝癌细胞的侵袭。低剂量的Mab 36还能为小鼠提供完全抵抗伯氏疟原虫子孢子攻击的保护作用。线性表位作图显示,Mab 36识别的表位特异性完全被先前显示在体内与抵抗恶性疟原虫或伯氏疟原虫子孢子感染相关的其他单克隆抗体所涵盖。这些结果表明,针对特定CS蛋白重复表位产生高亲和力IgM抗体的能力对于引发抵抗疟疾感染的保护作用可能很重要。

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引用本文的文献

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Circumsporozoite protein as a potential target for antimalarials.环子孢子蛋白作为抗疟药物的潜在靶点。
Expert Rev Anti Infect Ther. 2015 Aug;13(8):923-6. doi: 10.1586/14787210.2015.1058709. Epub 2015 Jun 16.
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Why functional pre-erythrocytic and bloodstage malaria vaccines fail: a meta-analysis of fully protective immunizations and novel immunological model.
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PLoS One. 2010 May 19;5(5):e10685. doi: 10.1371/journal.pone.0010685.