Kan Qiuqi, Lin Xian, Li Tuofan, Ke Xianliang, Jian Xiaoqin, Hou Lidan, Zhang Wenyuan, Wan Zhimin, Xie Quan, Shao Hongxia, Ye Lilin, Ye Jianqiang, Qin Aijian, Zou Zhong, Chen Quanjiao
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China.
Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
J Med Virol. 2023 Mar;95(3):e28657. doi: 10.1002/jmv.28657.
Novel immune escape variants have emerged as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose of mAb G5 could significantly inhibit the viral burden in mice challenged with the mouse-adapted SARS-CoV-2 or SARS-CoV-2 Omicron BA.1 variant, as well as the body weight loss and cytokine release induced by mouse-adapted SARS-CoV-2. The refined epitope recognized by mAb G5 was identified as FKEELDKYF in the stem helix of subunit S2. In addition, a human-mouse chimeric mAb was generated based on the variable region of heavy chain and VL genes of mAb G5. Our study provides a broad antibody drug candidate against SARS-CoV-2 VOCs and reveals a novel target for developing pan-SARS-CoV-2 vaccines.
随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在全球范围内持续传播，新型免疫逃逸变体不断出现。许多变体在接种疫苗的人群中引发突破性感染，给当前针对刺突蛋白中受体结合域免疫显性的抗病毒策略带来巨大挑战。在此，我们发现一种新型的广谱中和单克隆抗体（mAb）G5在体外和体内均能有效抵御SARS-CoV-2变异株（VOCs）。单剂量的mAb G5能够显著抑制用小鼠适应型SARS-CoV-2或SARS-CoV-2奥密克戎BA.1变异株攻击的小鼠体内的病毒载量，以及由小鼠适应型SARS-CoV-2诱导的体重减轻和细胞因子释放。mAb G5识别的精细表位被确定为亚基S2茎螺旋中的FKEELDKYF。此外，基于mAb G5的重链可变区和VL基因构建了人-鼠嵌合单克隆抗体。我们的研究提供了一种针对SARS-CoV-2 VOCs的广谱抗体药物候选物，并揭示了开发泛SARS-CoV-2疫苗的新靶点。
