A major goal of SARS-CoV-2 vaccination is the induction of neutralizing antibodies (nAbs) capable of blocking infection by preventing interaction of the SARS-CoV-2 Spike protein with ACE2 on target cells. Cocktails of monoclonal nAbs can reduce the risk of severe disease if administered early in infection. However, multiple variants of concern (VOCs) have arisen during the pandemic that may escape from nAbs. In this issue of the JCI, Jia Zou, Li Li, and colleagues used yeast display libraries to identify mAbs that bind to Spike proteins with a vast array of single amino acid substitutions. The authors identified mutation-resistant monoclonal nAbs for potential use as therapeutics. Multimerization further improved the potency of selected nAbs. These findings suggest a way forward in development of better nAb cocktails. However, the emergence of the highly mutated omicron (B.1.1.529) variant heightens the importance of finding effective anti–SARS-CoV-2 nAb therapeutics despite rapid viral evolution.

中文翻译：

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寻找抗逃逸抗 SARS-CoV-2 中和抗体

SARS-CoV-2 疫苗接种的一个主要目标是诱导中和抗体 (nAb)，该中和抗体能够通过阻止 SARS-CoV-2 刺突蛋白与靶细胞上的 ACE2 相互作用来阻断感染。如果在感染早期施用单克隆抗体混合物可以降低患严重疾病的风险。然而，在大流行期间出现了多种可能从 nAb 中逃脱的令人担忧的变体 (VOC)。在本期JCI中，Jia Zou、Li Li 及其同事使用酵母展示文库来鉴定与带有大量单氨基酸取代的 Spike 蛋白结合的 mAb。作者确定了具有潜在治疗用途的抗突变单克隆抗体。多聚化进一步提高了所选 nAb 的效力。这些发现为开发更好的 nAb 鸡尾酒提供了一条前进的道路。然而，尽管病毒进化迅速，但高度突变的 omicron (B.1.1.529) 变体的出现凸显了寻找有效的抗 SARS-CoV-2 nAb 疗法的重要性。