Gu Chunyin, Cao Xiaodan, Wang Zongda, Hu Xue, Yao Yanfeng, Zhou Yiwu, Liu Peipei, Liu Xiaowu, Gao Ge, Hu Xiao, Zhang Yecheng, Chen Zhen, Gao Li, Peng Yun, Jia Fangfang, Shan Chao, Yu Li, Liu Kunpeng, Li Nan, Guo Weiwei, Jiang Guoping, Min Juan, Zhang Jianjian, Yang Lu, Shi Meng, Hou Tianquan, Li Yanan, Liang Weichen, Lu Guoqiao, Yang Congyi, Wang Yuting, Xia Kaiwen, Xiao Zheng, Xue Jianhua, Huang Xueyi, Chen Xin, Ma Haixia, Song Donglin, Pan Zhongzong, Wang Xueping, Guo Haibing, Liang Hong, Yuan Zhiming, Guan Wuxiang, Deng Su-Jun
Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People's Republic of China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China.
MAbs. 2021 Jan-Dec;13(1):1930636. doi: 10.1080/19420862.2021.1930636.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）可引发2019冠状病毒病（COVID-19），在感染过程中，该病毒通过其刺突1蛋白与宿主细胞受体血管紧张素转换酶2（hACE2）相互作用。病毒序列公布后，我们仅用10天时间，就在噬菌体-酵母（PtY）展示平台上，从抗体文库中鉴定出两种针对SARS-CoV-2受体结合域（RBD）的高效抗体。我们的先导抗体JMB2002目前正在进行1期临床试验（ChiCTR2100042150），它对hACE2与多种SARS-CoV-2变体的RBD结合表现出广谱阻断活性，这些变体包括B.1.351，据报道该变体对康复期血浆、疫苗血清及一些临床阶段中和抗体的中和作用具有更强的抗性。此外，JMB2002在恒河猴疾病模型中已证明具有完全的预防和强效治疗效果。使用JMB2002对SARS-CoV-2进行预防和治疗对策干预，可能会减缓当前出现的SARS-CoV-2变体的传播，并更有效地控制COVID-19大流行。
