对抗SARS-CoV-2的人类抗体具有强烈的中和和保护作用
Seth J Zost1, Pavlo Gilchuk1, James Brett Case2
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Nature
|July 16, 2020
概括
研究人员确定了针对SARS-CoV-2尖端蛋白的强有力的人类单克隆抗体. 这些抗体通过阻断ACE2相互作用来中和病毒,并在动物模型中提供保护,指导疫苗和治疗开发.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 由SARS-CoV-2引起的COVID-19流行病构成了严重的全球健康威胁,医疗对策有限.
- 目前缺乏对SARS-CoV-2幽默免疫的全面了解.
研究的目的:
- 分析针对SARS-CoV-2尖端糖蛋白的人类单克隆抗体.
- 识别具有强大的中和活性和阻断ACE2相互作用的能力的抗体.
- 为疫苗设计和免疫治疗剂选择提供基于结构的框架.
主要方法:
- 对抗SARS-CoV-2尖端 (S) 蛋白质的一大组人类单克隆抗体的分析.
- 竞争结合,结构和功能研究以表征抗体结合部位和构造状态.
- 使用小鼠模型和 rhesus 来评估抗体疗效的体内研究.
主要成果:
- 确定了几种强大的中和单克隆抗体,这些抗体阻断了S蛋白的受体结合域 (SRBD) 与ACE2的相互作用.
- 将抗体分组为分类,识别S三元体的不同表位和构造状态.
- 通过同时结合的抗体 (COV2-2196和COV2-2130) 证明了协同的中和作用.
- 在小鼠模型中显示出对SARS-CoV-2感染,体重减轻,病毒负担和肺炎的保护作用.
- 通过使用强大的ACE2阻断单克隆抗体作为单疗法,在 rhesus中得到了保护.
结论:
- 在SARS-CoV-2 SRBD上确定了保护性表位.
- 为开发有效的SARS-CoV-2疫苗和免疫疗法建立了基于结构的框架.
- 突出了特定单克隆抗体的预防和治疗潜力.
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