With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

随着传染性增强和潜在耐药性的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种的出现，需要具有广泛抑制活性的抗体和疫苗。在这里，我们开发了一组中和性抗 SARS-CoV-2 单克隆抗体 (mAb)，这些抗体将刺突蛋白的受体结合域结合在不同的表位上，并阻止病毒与其宿主受体、人血管紧张素转换酶 2 (hACE2) 的附着。 ）。尽管几种有效的中和单克隆抗体可保护 K18-hACE2 转基因小鼠免受祖先 SARS-CoV-2 菌株引起的感染，但其他单克隆抗体会在体内诱导逃逸变异或失去针对新出现菌株的中和活性。一种 mAb SARS2-38 能够有效中和所有测试的相关 SARS-CoV-2 变体，并保护小鼠免受多种 SARS-CoV-2 毒株的攻击。结构分析表明，SARS2-38 与受体结合基序邻近的保守表位结合。因此，使用结合保守刺突表位的中和抗体进行治疗或诱导可能会限制针对新出现的 SARS-CoV-2 变体的疗法或疫苗效力的丧失。