Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
State Key Laboratory for Emerging Infectious Diseases, Carol Yu Center for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Cell Infect Microbiol. 2023 Aug 14;13:1213806. doi: 10.3389/fcimb.2023.1213806. eCollection 2023.
Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.
We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The effectiveness of WKS13 was evaluated in a hamster model.
Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant.
Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.
针对 SARS-CoV-2 刺突蛋白的治疗性单克隆抗体（mAbs）已在临床试验中显示出可改善重症 COVID-19 患者的预后。然而，具有刺突蛋白突变的新型变体可能使许多现有的 mAbs 失效。
我们使用杂交瘤细胞产生 mAbs，这些细胞是通过用刺突蛋白三聚体和受体结合域（RBD）免疫的小鼠产生的。该 mAb 组被筛选用于针对不同 SARS-CoV-2 变体的结合和中和活性。在仓鼠模型中评估了 WKS13 的有效性。
在 960 个克隆中，我们鉴定出 18 种能够结合刺突蛋白的 mAbs。其中 10 种 mAbs 可以附着在 RBD 上，其中 5 种对原始株具有中和活性，并且可以阻断刺突蛋白与人 ACE2 之间的结合。这些 mAbs 之一，WKS13，对所有关注的变体（VOCs）具有广泛的中和活性，包括奥密克戎变体。Delta 变体感染的仓鼠中，鼠源或人源化的 WKS13 均可降低肺部病毒载量。
我们的数据表明，广谱高活性 mAbs 可从免疫小鼠中产生，在 Fc 区域人源化后可用于人类。我们的方法代表了一种用于产生针对新型变体的治疗性 mAbs 的通用且快速的策略。
