Prevention of human rhinovirus infection by multivalent Fab molecules directed against ICAM-1
Prevention of human rhinovirus infection by multivalent Fab molecules directed against ICAM-1
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DOI：
10.1128/aac.47.5.1503-1508.2003
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发表时间：
2003-05-01
影响因子：
4.9
通讯作者：
Fang, F
中科院分区：
文献类型：
--
作者：
Charles, CH;Luo, GX;Fang, F
我们已经开发了通过制备二价、三价或四价重组多肽来提高亲合力的技术。我们设计了三重蛋白，由抗体的Fab片段与源自人免疫球蛋白D的铰链融合组成，该铰链进一步与源自人卷曲螺旋蛋白的聚合结构域连接。我们在这里报告的应用程序，这种方法与Fab结构域针对主要的人鼻病毒受体，细胞间粘附分子1（ICAM-1）。在细菌中产生多价抗ICAM-1分子，并以高产率纯化为可溶性预组装均质蛋白。这些蛋白在体外成功地阻断了鼻病毒感染，其效率从单体增加到二聚体、三聚体和四聚体。这些多价抗体的解离速率降低以及它们在预防鼻病毒感染中的改善的功效为产生针对人鼻病毒（大多数普通感冒的病原体）的预防性和治疗性分子提供了基础。
We have developed a technology for improving avidity by making bivalent, trivalent, or tetravalent recombinant polypeptides. We designed tripartite proteins consisting of the Fab fragment of an antibody fused with a hinge derived from human immunoglobulin D that was further linked to polymerization domains derived from human coiled-coil proteins. We report here on the application of this method with a Fab domain directed against the major human rhinovirus receptor, intercellular adhesion molecule 1 (ICAM-1). Multivalent anti-ICAM-1 molecules were produced in bacteria and purified as soluble preassembled homogeneous proteins at high yield. These proteins successfully blocked rhinovirus infection in vitro, with the efficiency increasing from monomer to dimer, trimer, and tetramer. The diminished dissociation rate of these multivalent antibodies and their improved efficacy in preventing rhinovirus infection provide a foundation for producing prophylactic and therapeutic molecules against human rhinovirus, the causative agent of the majority of common colds.