Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.
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DOI：
10.1126/science.abh1139
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发表时间：
2021-08-13
期刊：
影响因子：
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通讯作者：
Wilson IA
中科院分区：
文献类型：
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作者：
Yuan M;Huang D;Lee CD;Wu NC;Jackson AM;Zhu X;Liu H;Peng L;van Gils MJ;Sanders RW;Burton DR;Reincke SM;Prüss H;Kreye J;Nemazee D;Ward AB;Wilson IA
针对野生型SARS-CoV-2刺突蛋白的受体结合位点(RBS)而产生的中和抗体(NAB)对最近关注的变种通常效果较差。RBS残基E484、K417和N501在南非(B.1.351)和巴西(P.1)首次描述的变异中发生突变。我们分析了它们对新冠肺炎患者NAB中血管紧张素转换酶2结合及K417N和E484K突变的影响。两个最常见的抗体家族(IGHV3-53/3-66和IGHV1-2)的结合和中和都可以通过交替的结合模式与RBS结合，但K417N和/或E484K取消了这两个家族的结合和中和。这些效应可以通过它们与苏格兰皇家银行nabs的广泛相互作用在结构上得到解释。然而，对更保守的、交叉中和的CR3022和S309位点的NAB基本上没有受到影响。这一结果对下一代疫苗和抗体疗法具有重要意义。
Neutralizing antibodies (nAbs) elicited against the receptor-binding site (RBS) of the spike protein of wild-type SARS-CoV-2 are generally less effective against recent variants of concern. RBS residues E484, K417 and N501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on ACE2 binding and K417N and E484K mutations on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternate binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.