超强的人类抗体通过多种机制对SARS-CoV-2的挑战进行保护
M Alejandra Tortorici1,2, Martina Beltramello3, Florian A Lempp4
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|September 25, 2020
概括
两种强效的中和抗体S2E12和S2M11被确定用于对抗严重急性呼吸综合征冠状病毒2 (SARS-CoV-2). 这些抗体保护子,并显示出抗体尾酒在预防和治疗SARS-CoV-2感染方面具有前景.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 引起的全球流行病需要制定有效的治疗策略.
- 现有治疗方法需要加强以控制病毒传播和减轻死亡人数.
研究的目的:
- 针对SARS-CoV-2的新型人类中和抗体的分离和特征.
- 在临床前模型中评估这些抗体的治疗潜力.
- 阐明这些抗体在分子水平上的作用机制.
主要方法:
- 从感染个体中分离和鉴定中和抗体.
- 在活体中使用子模型感染SARS-CoV-2的疗效研究.
- 用冷电子显微镜来确定抗体与抗原相互作用的结构基础.
- 对各种SARS-CoV-2分离体的抗体中和幅度的评估.
- 评估抗体介导的效应器功能.
主要成果:
- 发现了两个超强的中和抗体S2E12和S2M11.
- 在感染SARS-CoV-2的仓鼠中,S2E12和S2M11显示出保护作用.
- 结构分析显示,这两种抗体都阻断了ACE2结合,而S2M11则在封闭的形状下进一步稳定了尖端蛋白.
- 包括S2M11,S2E12或S309在内的抗体混合物广泛中和了循环中的SARS-CoV-2分离物.
- 这些抗体激活了效应器功能.
结论:
- 已发现的抗体S2E12和S2M11代表了SARS-CoV-2预防和治疗的有希望的候选者.
- 抗体尾酒提供了一种扩大中和克服病毒逃生突变的策略.
- 这些发现支持针对SARS-CoV-2的基于抗体的临床干预措施的开发.
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