Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2
Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2
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DOI：
10.1038/s41586-021-04388-0
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发表时间：
2021-12-23
期刊：
影响因子：
64.8
通讯作者：
Ho, David D.
中科院分区：
文献类型：
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作者：
Liu, Lihong;Iketani, Sho;Ho, David D.
SARS-CoV-2的B.1.1.529/Omicron变体最近才在南部非洲被发现，但其随后在区域和全球范围内广泛传播(1)。预计在未来几周内它将成为主导(2)，可能是由于传播性增强。该变异的一个显著特征是大量刺突突变(3)，这对当前COVID-19疫苗和抗体疗法的有效性构成威胁(4)。我们的研究结果放大了这种担忧。在这里，我们发现B.1.1.529不仅对COVID-19康复患者的血清中和具有明显的抗性，而且对接种了四种广泛使用的COVID-19疫苗之一的个体也具有明显的抗性。即使是接种了疫苗并接受了加强剂量的mrna疫苗的个体的血清，也显示出对B.1.1.529的中和活性大大降低。通过评估一组针对刺突蛋白上所有已知表位簇的单克隆抗体，我们注意到19种抗体中有17种的活性被取消或受损，包括那些目前已被批准或批准用于患者的抗体。此外，我们还发现了四种新的刺突突变（S371L, N440K， G446S和Q493R），它们赋予B.1.1.529更大的抗体抗性。Omicron变体对许多现有的COVID-19疫苗和疗法构成严重威胁，迫使开发新的干预措施，预测SARS-CoV-2的进化轨迹。
The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally(1). It is expected to become dominant in the coming weeks(2), probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations(3) that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies(4). This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.