Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School , Pittsburgh, PA, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill , Chapel Hill, NC, USA.
MAbs. 2020 Jan 1;12(1):1778435. doi: 10.1080/19420862.2020.1778435.
Effective therapies are urgently needed for COVID-19. Here we describe the identification of a new stable human immunoglobulin G1 heavy-chain variable (VH) domain scaffold that was used for the construction of a large library, lCAT6, of engineered human VHs. This library was panned against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. Two VH domains (VH ab6 and VH m397) were selected and fused to Fc for increased half-life in circulation. The VH-Fc ab6 and m397 specifically neutralized SARS-CoV-2 with high potencies (50% neutralization at 0.35 µg/ml and 1.5 µg/ml, respectively) as measured by two independent replication-competent virus neutralization assays. Ab6 and m397 competed with ACE2 for binding to RBD, suggesting a competitive mechanism of virus neutralization. These VH domains may have potential applications for prophylaxis and therapy of COVID-19 alone or in combination, as well as for diagnosis and as tools for research.
我们需要有效的疗法来应对 COVID-19。在这里，我们描述了一种新的稳定的人免疫球蛋白 G1 重链可变（VH）结构域支架的鉴定，该支架用于构建一个大型的工程化人 VH 文库 lCAT6。该文库针对 SARS-CoV-2 刺突（S）糖蛋白的受体结合域（RBD）进行了筛选。选择了两个 VH 结构域（VH ab6 和 VH m397）并与 Fc 融合，以增加在循环中的半衰期。VH-Fc ab6 和 m397 通过两种独立的复制型病毒中和测定，以高效价（分别在 0.35µg/ml 和 1.5µg/ml 时达到 50%中和）特异性中和 SARS-CoV-2。Ab6 和 m397 与 ACE2 竞争结合 RBD，提示病毒中和的竞争机制。这些 VH 结构域可能具有单独或联合用于 COVID-19 的预防和治疗、诊断以及研究工具的潜在应用。
