SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.

Qianqian Li1 Jianhui Nie1 Jiajing Wu1 Li Zhang1 Ruxia Ding1 Haixin Wang1 Yue Zhang1 Tao Li1 Shuo Liu1 Mengyi Zhang1 Chenyan Zhao1 Huan Liu1 Lingling Nie1 Haiyang Qin1 Meng Wang1 Qiong Lu1 Xiaoyu Li1 Junkai Liu1 Haoyu Liang1 Yi Shi2 Yuelei Shen3 Liangzhi Xie4 Linqi Zhang5 Xiaowang Qu6 Wenbo Xu7 Weijin Huang8 Youchun Wang9
Affiliations 9 institutions
  1. 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.
  2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
  3. Beijing Biocytogen Co., Ltd., Beijing 101111, China.
  4. Beijing Antibody Research Key Laboratory, Sino Biological Inc., Building 9, Jing Dong Bei Technology Park, No. 18 Ke Chuang 10th St., BDA, Beijing 100176, China.
  5. Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
  6. Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou 423000, China. Electronic address: [email protected].
  7. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China. Electronic address: [email protected].
  8. 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. Electronic address: [email protected].
  9. 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. Electronic address: [email protected].

Abstract

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.

Supporting text Virus Host Location
501Y.V2 1 E484K 1 immune escape 5 infectivity 7 K417N 1 mutation 222 N501Y 3 neutralizing antibody 5 receptor binding region 1 SARS-CoV-2 550 Immune Evasion 25 Angiotensin-Converting Enzyme 2 177 Antibodies, Monoclonal 26 Antibodies, Neutralizing 80 Antigens, Viral 49 Cell Line, Tumor 12 COVID-19 425 HEK293 Cells 61 Humans 1440 Mutation 209 SARS-CoV-2 453

Evidence records

2 total
Functional Mechanism
2 records · 2 evidence types
Evidence type
1 records
OVE4633
Key finding

Enhanced infectivity of SARS-CoV-2 501Y.V2 variants toward murine ACE2-expressing cells suggests potential human-to-mouse spillback.

Virus
Host
Location
Not specified
Supporting text

The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice.

Method
pseudotyped virus infectivity assay
Receptors
ACE2
Evidence type
1 records
OVE4630
Key finding

E484K and N501Y mutations in the spike receptor-binding domain of SARS-CoV-2 501Y.V2 variants confer neutralization resistance, indicating immune escape adaptation.

Virus
Host
Not specified
Location
Not specified
Supporting text

The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike.

Genes or proteins
spike | receptor-binding domain
Mutations
E484K | N501Y
Mechanism types
immune escape