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通过SARS-CoV-2的P.1菌株进行抗体逃避

Wanwisa Dejnirattisai¹, Daming Zhou², Piyada Supasa¹

¹Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

|April 14, 2021

概括

新的SARS-CoV-2变种如P.1和B.1.351具有影响ACE2结合的突变. 单克隆抗体222可以中和这些变体,而它的轻链可以恢复抗体对它们的有效性.

科学领域:

病毒学
免疫学
结构生物学

背景情况:

在全球范围内,SARS-CoV-2 疫情需要进行疫苗接种.
目前的疫苗针对的是早期SARS-CoV-2分离的尖端蛋白.
新兴变种 (P.1,B.1.351,B.1.1.7) 具有多个尖端突变,包括在ACE2结合部位的突变.

研究的目的:

研究SARS-CoV-2变异对ACE2结合亲和力和中和性的影响.
评估单克隆抗体 (mAb) 222对新出现的SARS-CoV-2变种的疗效.
了解mAb 222中和的结构基础及其恢复抗体功能的潜力.

主要方法:

对SARS-CoV-2尖端蛋白变体的结构分析.
对突变尖端蛋白的ACE2结合 afinity 的评估.
使用自然感染或接种疫苗的个体和单克隆抗体的血清进行中和测试.
对mAb 222与尖端蛋白的相互作用进行结构分析.

主要成果:

在P.1和B.1.351中发生的突变,特别是E484K,K417N/T和N501Y三重组,增加了ACE2结合亲和力.
与B.1.351相比,P.1对抗体中和的抵抗性较低,这表明非受体结合域 (RBD) 突变的影响.
尽管mAb 222在ACE2结合部位内的向突变,但它有效地中和了P. 1, B.1. 351和B.1. 1.7变种.
结构洞察力揭示了mAb 222如何中和多个变体,并证明其轻链可以恢复对公共抗体的中和.

结论:

SARS-CoV-2 变异突变显著影响了 ACE2 结合和抗体中和敏感性.
单克隆抗体222对关键的SARS-CoV-2变体具有广泛的中和活性.
对mAb 222尖峰相互作用的结构理解为开发广泛的保护性抗体疗法提供了基础.

关键词:

P.1 其他在RBD 冠状病毒在VH3-53中抗体逃生方式中和一个结构变种

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