SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern

McCallum, Matthew; Bassi, Jessica; De Marco, Anna; Chen, Alex; Walls, Alexandra C; Di Iulio, Julia; Tortorici, M Alejandra; Navarro, Mary-Jane; Silacci-Fregni, Chiara; Saliba, Christian; Sprouse, Kaitlin R; Agostini, Maria; Pinto, Dora; Culap, Katja; Bianchi, Siro; Jaconi, Stefano; Cameroni, Elisabetta; Bowen, John E; Tilles, Sasha W; Pizzuto, Matteo Samuele; Guastalla, Sonja Bernasconi; Bona, Giovanni; Pellanda, Alessandra Franzetti; Garzoni, Christian; Van Voorhis, Wesley C; Rosen, Laura E; Snell, Gyorgy; Telenti, Amalio; Virgin, Herbert W; Piccoli, Luca; Corti, Davide; Veesler, David

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.