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

• Published in: Science 2021-08, Vol.373 (6555), p.648-654
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 2019-nCoV Vaccine mRNA-1273; ACE2; Amino Acid Substitution; Angiotensin-converting enzyme 2; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Antigens, Viral - immunology; Binding; BNT162 Vaccine; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; COVID-19 Vaccines - immunology; Cryoelectron Microscopy; Domains; Glycoproteins; Humans; Immune Evasion; Mass spectrometry; Models, Molecular; Monoclonal antibodies; Mutation; Neutralization; Neutralization Tests; Neutralizing; Pandemics; Peptides; Protein Conformation; Protein Domains; Protein Interaction Domains and Motifs; Protein Subunits - chemistry; Proteins; Receptors; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Vaccines; Viral diseases; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abi7994

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.