Pan Yongbing, Du Jianhui, Liu Jia, Wu Hai, Gui Fang, Zhang Nan, Deng Xiaojie, Song Gang, Li Yufeng, Lu Jia, Wu Xiaoli, Zhan ShanShan, Jing Zhaofei, Wang Jiong, Yang Yimin, Liu Jianbang, Chen Ying, Chen Qin, Zhang Huanyu, Hu Hengrui, Duan Kai, Wang Manli, Wang Qisheng, Yang Xiaoming
National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd., Wuhan, Hubei, China.
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
Cell Discov. 2021 Jul 27;7(1):57. doi: 10.1038/s41421-021-00295-w.
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (K = 4.76 nM for the S1 protein, IC = 6 ng/mL for pseudoviruses, and IC = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11-RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.
随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）持续威胁全球公共卫生，迫切需要开发有效的干预措施。中和抗体（nAbs）在预防和治疗SARS-CoV-2感染方面具有巨大潜力。在本研究中，从由8名新冠肺炎康复患者的外周血单个核细胞（PBMC）构建的两个噬菌体展示免疫文库中分离出10种中和抗体。其中8种由免疫球蛋白重链基因可变区（IGHV）3-66或IGHV3-53基因编码的重链组成，它们识别受体结合域（RBD）上的相同表位，而其余两种结合不同表位。在这10种抗体中，2B11对原始野生型（WT）SARS-CoV-2病毒表现出最高亲和力和中和效力（S1蛋白的K值为4.76 nM，假病毒的IC50为6 ng/mL，真实病毒的IC50为1 ng/mL），并且对B.1.1.7假病毒具有强大的中和能力。此外，靶向RBD上不同表位的1E10对WT SARS-CoV-2及其变体B.1.1.7、B.1.351和P.1表现出不同的中和效率。2B11-RBD复合物的晶体结构表明，2B11的表位与血管紧张素转换酶2（ACE2）结合位点高度重叠。使用AdV5-hACE2转导小鼠进行的2B11体内实验显示出对SARS-CoV-2令人鼓舞的治疗和预防效果。综上所述，我们的结果表明，高效的SARS-CoV-2中和抗体2B11可用于对抗WT SARS-CoV-2和B.1.1.7变体，或与不同表位靶向的中和抗体（如1E10）联合使用以对抗SARS-CoV-2变体。
