Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery.

中文翻译：

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在降低的 pH 值下筛选抗体可以优先选择针对 SARS-CoV-2 的强效中和抗体

抗病毒单克隆抗体 (mAb) 的发现使基于抗体的抗病毒疗法的开发成为可能。传统的抗病毒 mAb 发现依赖于抗体与病毒抗原之间的亲和力来发现有效的中和抗体，但这些方法效率低下，因为许多高亲和力 mAb 没有中和活性。我们试图确定在降低的 pH 值下筛选抗 SARS-CoV-2 mAb 是否可以提供更有效的中和抗体发现。我们在生理 pH (7.4) 和降低的 pH (4.5) 下挖掘了康复期 COVID-19 患者的抗体反应，揭示 SARS-CoV-2 中和抗体优先富集 pH 4.5 酵母展示种类。结构分析显示，一种名为 LP5 的强效新抗体通过独特的结合识别模式靶向 SARS-CoV-2 N 端域超位点。我们的数据与先前研究的证据相结合，支持在 pH 4.5 下筛选抗体，以加速抗病毒中和抗体的发现。