寨卡病毒特异性抗体保护的结构基础
Haiyan Zhao1, Estefania Fernandez2, Kimberly A Dowd3
1Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Cell
|August 1, 2016
概括
研究人员开发出针对寨卡病毒 (ZIKV) 的单克隆抗体,可以中和寨卡病毒感染. 这些抗体的被动转移保护了小鼠,这表明ZIKV预防药物和疫苗的途径.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 在怀孕期间感染寨卡病毒 (ZIKV) 是由于严重的先天性异常而造成的全球性健康风险.
- 开发有效的ZIKV防治措施对于公共健康至关重要.
研究的目的:
- 开发和描述针对寨卡病毒的新型单克隆抗体 (mAbs).
- 通过中和抗体识别ZIKV表位.
- 评估ZIKV特异性抗体的体内疗效.
主要方法:
- 产生和选六个小鼠单克隆抗体来对抗ZIKV.
- 进行X射线结晶学和结合分析,以确定ZIKV包膜蛋白DIII上的抗体表位.
- 在小鼠感染ZIKV模型中的体内被动转移研究.
主要成果:
- 在6种开发的mAbs (ZV-48,ZV-54,ZV-64,ZV-67) 中,有4种是ZIKV特异性的,并且对各种ZIKV菌株表现出中和作用.
- 在封膜蛋白的DIII区域发现了三种不同的表位,它们被不同的mAbs所准.
- 在小鼠模型中被动转移DIII侧脊特异性的中和mAbs给予了保护.
结论:
- ZIKV包膜蛋白的DIII区域是多种抗体的目标,具有不同的中和能力.
- 这些发现支持对孕妇的预防性抗体和表位特异性ZIKV疫苗的开发.
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