nature

当前位置: Nature » 蛋白&蛋白质组学 » 正文

Nature:具有广泛抗登革热活性的抗体的结构

标签:X射线 晶体学
摘要 : 人们最近发现了一大类具有广泛中和活性的人类抗体,它们能够强力中和全部四个登革热病毒血清型。

 人们最近发现了一大类具有广泛中和活性的人类抗体,它们能够强力中和全部四个登革热病毒血清型。这一发现让我们看到一个希望:也许有可能设计一种疫苗,来提供针对该疾病的严重形式的保护作用。Alexander Rouvinski等人报告了与登革热病毒 “包膜蛋白-E”的可溶二聚物形式形成复合物的四种这类抗体的X-射线晶体结构。这些抗体能够识别一个“四元表位”(quaternary epitope),并且表现出针对全部四个病毒子类型的强烈中和活性。

登革热是由四个不同的flavivirus1血清型引起,其中感染390000000人年25%例症状并没有获得许可的疫苗是可用的。结构研究到目前为止表明抗原表位特别识别的血清型特异性人源抗体。我们最近从人类抗体中分离出能有效地中和四种血清型登革热病毒的抗体。我们用x-rays光研究了这些从2型登革病毒混合着包膜糖蛋白的这些广泛中和抗体。揭示了两者识别的决定因素是在血清型登革热病毒的抗体E-dimer表面,包括暴露的主链的E融合loop8和两个保守的糖链.

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Dengue disease is caused by four different flavivirus1 serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype2 . Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This ‘E-dimer-dependent epitope’ is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles’ heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.

对应Nature杂志: 2015年04月02日Nature杂志精选

来源: Nature 浏览次数:1

热门文章TOP

RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.