An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies.

An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies.
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DOI:
10.1038/s41591-021-01678-y
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发表时间:
2022-03
期刊:
影响因子:
82.9
通讯作者:
Diamond MS
Diamond MS
中科院分区:
医学1区
文献类型:
--
作者:
VanBlargan LA;Errico JM;Halfmann PJ;Zost SJ;Crowe JE Jr;Purcell LA;Kawaoka Y;Corti D;Fremont DH;Diamond MS

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严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的高传播性Omicron变体的出现令人担忧,B.1.1.529在这项研究中,我们测试了一组抗受体结合域单克隆抗体(mAb),这些抗体与Vir Biotechnology临床使用的抗体相对应(S309,VIR-7831(sotrovimab)的母体mAb),阿斯利康(COV 2 -2196和COV 2 -2130,AZD 8895和AZD 1061的亲本mAb),Regeneron(REGN 10933和REGN 10987)、Eli Lilly(LY-CoV 555和LY-CoV 016)和Celltrion(CT-P59)中和感染性B.1.1.529 Omicron分离株的能力。几种mAb(LY-CoV 555、LY-CoV 016、REGN 10933、REGN 10987和CT-P59)在Vero-TMPRSS 2和Vero-hACE 2-TMPRSS 2细胞中完全丧失了抗B.1.1.529病毒的中和活性,而其他mAb的活性降低(COV 2 -2196和COV 2 -2130组合,降低约12倍)或受影响极小(S309)。我们的研究结果表明,临床使用的几种但不是全部抗体可能会对Omicron变体失去效力。B.1.1.529新的体外数据表明,新的SARS-CoV-2 Omicron变异体很可能逃脱目前可用的大多数治疗性抗体的中和。
The emergence of the highly transmissible B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is concerning for antibody countermeasure efficacy because of the number of mutations in the spike protein. In this study, we tested a panel of anti-receptor-binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309, the parent mAb of VIR-7831 (sotrovimab)), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Eli Lilly (LY-CoV555 and LY-CoV016) and Celltrion (CT-P59) for their ability to neutralize an infectious B.1.1.529 Omicron isolate. Several mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987 and CT-P59) completely lost neutralizing activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (COV2-2196 and COV2-2130 combination, ~12-fold decrease) or minimally affected (S309). Our results suggest that several, but not all, of the antibodies in clinical use might lose efficacy against the B.1.1.529 Omicron variant. New in vitro data suggest that the new SARS-CoV-2 Omicron variant is likely to escape neutralization by most therapeutic antibodies currently available.
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