Cell
Volume 184, Issue 11, 27 May 2021, Pages 2939-2954.e9
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Article
Antibody evasion by the P.1 strain of SARS-CoV-2

https://doi.org/10.1016/j.cell.2021.03.055Get rights and content
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Highlights

  • Despite similar RBD mutations, P.1 is easier to neutralize than B.1.351

  • P.1, B.1.351, and B.1.1.7 partially or fully escape most VH3-53 antibodies

  • mAb 222 (VH3-53) retains neutralization against all three variants

  • Neutralization is restored in VH3-53 chimeric antibodies with mAb 222 LC

Summary

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Keywords

SARS-CoV-2
variant
neutralization
escape
antibody
RBD
P.1
VH3-53
structure
spike

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These authors contributed equally

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