Li Qianqian, Nie Jianhui, Wu Jiajing, Zhang Li, Ding Ruxia, Wang Haixin, Zhang Yue, Li Tao, Liu Shuo, Zhang Mengyi, Zhao Chenyan, Liu Huan, Nie Lingling, Qin Haiyang, Wang Meng, Lu Qiong, Li Xiaoyu, Liu Junkai, Liang Haoyu, Shi Yi, Shen Yuelei, Xie Liangzhi, Zhang Linqi, Qu Xiaowang, Xu Wenbo, Huang Weijin, Wang Youchun
Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, No. 31 Huatuo Street, Daxing District, Beijing 102629, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
Cell. 2021 Apr 29;184(9):2362-2371.e9. doi: 10.1016/j.cell.2021.02.042. Epub 2021 Feb 23.
The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的501Y.V2变体在刺突蛋白中含有多个突变，目前在南非占主导地位，并正在迅速传播到其他国家。在此，对18种假型病毒进行的实验表明，501Y.V2变体在多种细胞类型中不会增加感染性，但在过表达小鼠血管紧张素转换酶2（ACE2）的细胞中除外，在该细胞中观察到感染性显著增加。值得注意的是，501Y.V2变体对17种中和单克隆抗体中的12种的敏感性大幅降低，康复患者和免疫小鼠血清对这些变体的中和能力也有所降低。中和抗性主要由刺突蛋白受体结合域中的E484K和N501Y突变引起。在过表达小鼠ACE2的细胞中增强的感染性表明501Y.V2变体有可能传播到小鼠。此外，我们检测到的501Y.V2变体的中和抗性表明单克隆抗体和疫苗的效力可能受损。
