Cell
Volume 184, Issue 9, 29 April 2021, Pages 2362-2371.e9
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Article
SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape

https://doi.org/10.1016/j.cell.2021.02.042Get rights and content
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Highlights

  • 501Y.V2 showed no higher infectivity in cells with hACE2 comparing to 614G variant

  • 501Y.V2 showed increased infectivity in cells with mACE2 compared to 614G variant

  • 501Y.V2 escaped neutralization by most of neutralizing monoclonal antibodies

  • 501Y.V2 significantly compromised the inhibitory effects of polyclonal antibodies

Summary

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.

Keywords

SARS-CoV-2
mutation
receptor binding region
infectivity
neutralizing antibody
immune escape
501Y.V2
N501Y
E484K
K417N

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