SARS-CoV-2 Omicron sublineages show comparable cell entry but differential neutralization by therapeutic antibodies.
SARS-CoV-2 Omicron sublineages show comparable cell entry but differential neutralization by therapeutic antibodies.
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DOI：
10.1016/j.chom.2022.04.017
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发表时间：
2022-08-10
影响因子：
30.3
通讯作者：
Hoffmann, Markus
中科院分区：
文献类型：
--
作者：
Arora, Prerna;Zhang, Lu;Krueger, Nadine;Rocha, Cheila;Sidarovich, Anzhalika;Schulz, Sebastian;Kempf, Amy;Graichen, Luise;Moldenhauer, Anna-Sophie;Cossmann, Anne;Dopfer-Jablonka, Alexandra;Behrens, Georg M. N.;Jaeck, Hans-Martin;Poehlmann, Stefan;Hoffmann, Markus
SARS-CoV-2的Omicron变体以前所未有的效率逃避抗体介导的中和。至少有三个Omicron亚系已被确定-BA.1，BA. 2，和BA. 3-和BA. 2表现出增加的传递性。然而，目前尚不清楚BA. 2是否与其他亚系在细胞进入和抗体介导的抑制方面不同。在这里，我们表明，BA.1，BA.2和BA.3进入和融合靶细胞具有相似的效率和ACE 2依赖性的方式。然而，BA.2不能被用于COVID-19治疗的八种抗体中的七种有效中和，包括强力中和BA.1的Sotrovimab。相比之下，BA.2和BA.3（但不是BA.1）被Cilgavimab明显中和，这可能构成一种治疗选择。最后，在先前的两剂同源或异源疫苗接种后，所有亚系均被BNT 162 b2加强疫苗接种诱导的抗体中和并有效中和。总的来说，Omicron亚系显示出相当的细胞进入和疫苗诱导抗体的中和，但对治疗性抗体的敏感性不同。SARS-CoV-2 Omicron变异体包含至少三个主要的亚系，它们具有共享和独特的刺突蛋白突变。Arora等人显示亚系BA.1、BA.2和BA.3以相似的效率进入细胞，并被BNT 162 b2加强接种诱导的抗体中和，但在被治疗性抗体中和方面不同。
The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified—BA.1, BA.2, and BA.3—and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However, BA.2 was not efficiently neutralized by seven of eight antibodies used for COVID-19 therapy, including Sotrovimab, which robustly neutralized BA.1. In contrast, BA.2 and BA.3 (but not BA.1) were appreciably neutralized by Cilgavimab, which could constitute a treatment option. Finally, all sublineages were comparably and efficiently neutralized by antibodies induced by BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination. Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies. The SARS-CoV-2 Omicron variant contains at least three main sublineages that harbor shared and unique spike protein mutations. Arora et al. show that sublineages BA.1, BA.2, and BA.3 enter cells with similar efficiency and are comparably neutralized by antibodies induced by BNT162b2 booster vaccination but differ regarding neutralization by therapeutic antibodies.
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影响因子：
64.8
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影响因子：
64.5
作者：
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64.5
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影响因子：
8.8
作者：
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通讯作者：
Pöhlmann S