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广泛中和的阿尔法病毒抗体在E2上结合并抑制进入和退出

Julie M Fox¹, Feng Long², Melissa A Edeling³

¹Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

|November 11, 2015

概括

研究人员发现了广泛中和的单克隆抗体 (MAbs) 对奇孔尼亚和相关的阿尔法病毒有效. 这些抗体向保存的病毒表位,提供针对这些全球健康威胁的新疫苗和治疗方法的潜力.

科学领域:

病毒学
免疫学
结构生物学

背景情况:

chikungunya 病毒 (CHIKV) 是一种引起广泛爆发的重要类型的 arbovirus.
阿尔法病毒具有结构上的相似性,这表明它们有可能进行交叉中和.

研究的目的:

确定针对CHIKV的广泛中和单克隆抗体 (MAbs).
描述这些MAbs的表位和作用机制.
探索对抗多种阿尔法病毒的治疗潜力.

主要方法:

对小鼠和人类MAB进行查,以防治CHIKV.
在体外和体内中和测试.
氨酸扫描突变和功能测试.
电子显微镜 (cryo-EM) 的结构分析.

主要成果:

一些MAbs表现出对CHIKV,Mayaro和O'nyong'nyong病毒的抑制活性.
在小鼠中被动转移MAb提供了保护.
MAbs针对E2糖蛋白B域的保存表位,阻止病毒的进入和退出.
结构分析显示MAb结合会诱导尖端交叉链接.

结论:

针对E2糖蛋白B域的广泛中和MAbs对多个alphavirus具有有效性.
保存的表位是开发通用阿尔法病毒疫苗和治疗药物的有希望的目标.

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