Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization

Abstract

The relative resistance of SARS-CoV-2 variants B.1.1.7 and B.1.351 to antibody neutralization has been described recently. We now 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 (3.4 fold) and vaccinee sera (3.8-4.8 fold). The cryo-electron microscopy structure of a soluble prefusion-stabilized spike reveals the P.1 trimer to adopt exclusively a conformation in which one of the receptor-binding domains is in the "up" position, with the functional impact of mutations appearing to arise from local changes instead of global conformational alterations. The P.1 variant threatens current antibody therapies but less so the protective efficacy of our vaccines.

Figure 1.. Neutralization of BZΔ10 and P.1 by mAbs, convalescent plasma, and vaccinee sera.

See also Figures S1. (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.

Figure 2.. Cryo-EM Structure of the P.1 Spike

See also Figure S2 and Table S1. (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.