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. 2021 May 12;29(5):747-751.e4.
doi: 10.1016/j.chom.2021.04.007. Epub 2021 Apr 18.

Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization

Pengfei Wang  1 , Ryan G Casner  2 , Manoj S Nair  3 , Maple Wang  3 , Jian Yu  3 , Gabriele Cerutti  2 , Lihong Liu  3 , Peter D Kwong  4 , Yaoxing Huang  3 , Lawrence Shapiro  5 , David D Ho  6
Affiliations

Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization

Pengfei Wang et al. Cell Host Microbe. .

Abstract

The emergence of SARS-CoV-2 variants has raised concerns about altered sensitivity to antibody-mediated immunity. The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been recently investigated. We report that another emergent variant from Brazil, P.1, is not only refractory to multiple neutralizing monoclonal antibodies but also more resistant to neutralization by convalescent plasma and vaccinee sera. The magnitude of resistance is greater for monoclonal antibodies than vaccinee sera and evident with both pseudovirus and authentic P.1 virus. The cryoelectron microscopy structure of a soluble prefusion-stabilized spike reveals that the P.1 trimer adopts exclusively a conformation in which one of the receptor-binding domains is in the "up" position, which is known to facilitate binding to entry receptor ACE2. The functional impact of P.1 mutations thus appears to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so protective vaccine efficacy.

Keywords: NTD; P.1; RBD; SARS-CoV-2; antibody; convalescent plasma; mutation; neutralization; vaccine; variant.

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Conflict of interest statement

Declaration of interests P.W., J.Y., M.N., Y.H., L.L., and D.D.H. are inventors on a provisional patent application on mAbs to SARS-CoV-2.

Figures

None
Graphical abstract
Figure 1
Figure 1
Neutralization of BZD10 and P.1 by mAbs, convalescent plasma, and vaccinee sera (A) Changes in neutralization IC50 of select RBD and NTD mAbs. (B) Changes in reciprocal plasma neutralization ID50 values of convalescent plasma and reciprocal serum ID50 values for persons who received Moderna or Pfizer vaccine. Mean fold change in ID50 relative to the WT is written above the p values. Statistical analysis was performed using a Wilcoxon matched-pairs signed rank test. Two-tailed p values are reported. See also Figures S1.
Figure 2
Figure 2
Cryo-EM structure of the P.1 spike (A) Overall cryo-EM structure of the P.1 spike trimer with domains colored as shown in key, glycans shown in green, and mutations highlighted in red. Density is shown for the 3.8 Å reconstruction with the molecular model shown in ribbon representation. The left image shows a side view, with viral membrane located below, and the right image shows the view looking down on the spike apex. (B) NTD close up view. (C) RBD close up view. See also Figure S2 and Table S1.
See this image and copyright information in PMC

Update of

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