Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1–10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.

人单克隆抗体是安全、预防和治疗工具，可以快速开发，以帮助恢复 2019 年冠状病毒病 (COVID-19) 大流行造成的大规模健康和经济破坏。通过对 14 名 COVID-19 幸存者的 4,277 个 SARS-CoV-2 刺突蛋白特异性记忆 B 细胞进行单细胞分选，鉴定出 453 种中和抗体。最有效的中和抗体可识别刺突蛋白受体结合结构域，其次是识别 S1 结构域、刺突蛋白三聚体和 S2 亚基的抗体。其中只有 1.4% 能够以 1-10 ng/mL 的效力中和真正的病毒。最有效的单克隆抗体，旨在降低抗体依赖性增强的风险并延长半衰期，中和了真正的野生型病毒和包含 D614G、E484K 和 N501Y 取代的新兴变种。在缺乏 Fc 功能的情况下，分别在 0.25 和 4 mg/kg 剂量下观察到仓鼠模型的预防和治疗功效。