The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.

SARS-CoV-2 Omicron 变种惊人的高传播性和抗体逃避能力对当前疫苗和抗体免疫疗法的功效提出了巨大挑战。在这里，我们筛选了 34 种 BNT162b2 疫苗，并分离了源自 IGHV1-58 家族的公共广泛中和抗体 ZCB11。 ZCB11 专门针对病毒受体结合域，并中和所有相关的 SARS-CoV-2 变体，尤其是对真正的 Omicron 和 Delta 变体具有强大的效力。对 57 个自然发生的刺突突变或缺失进行的基于伪病毒的定位表明，S371L 会导致 11 倍的中和抗性，但可以通过 Omicron 变体中的补偿突变来挽救。 Cryo-EM 分析表明，ZCB11 重链主要与 Omicron 尖峰三聚体相互作用，其受体结合结构域处于向上构象，阻断 ACE2 结合。此外，预防性或治疗性 ZCB11 给药可保护金色叙利亚仓鼠肺部感染免受 Omicron 病毒攻击。这些结果表明，疫苗诱导的 ZCB11 是一种有前途的广泛中和抗体，可用于针对大流行 SARS-CoV-2 的生物医学干预措施。