Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines

Abstract

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in Spike could affect efficacy of those treatments. Hence, monitoring of mutations is necessary to forecast and readapt the inventory of therapeutics. Different phylogenetic nomenclatures have been used for the currently circulating SARS-CoV-2 clades. The Spike protein has different hotspots of mutation and deletion, the most dangerous for immune escape being the ones within the receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, and N501Y. Convergent evolution has led to different combinations of mutations among different clades. In this review we focus on the main variants of concern, that is, the so-called UK (B.1.1.7), South African (B.1.351) and Brazilian (P.1) strains.

Keywords: B.1.1.7; B.1.351; BNT162b2; COVID-19; LY-CoV555; LyCoV016; P.1; P.2; REGN10933; REGN10987; SARS-CoV-2; bamlanivimab; casirivimab; convalescent plasma; etesevimab; imdevimab; immune escape; mRNA-1273; mutations; neutralising antibody; polyclonal immunoglobulins.

FIGURE 1

Linearised representation of Single nucleotide polymorphisms (SNPs) and deletions commonly detected in the S1 and S2 domains of the Spike protein, with a focus on the receptor binding domain (RBD) and receptor binding motif (RBM). Circle size represents relative abundance of the mutation in worldwide genome repositories as of January 2021. Mutations within RBD are represented on grey background