SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern
2021; American Association for the Advancement of Science; Volume: 373; Issue: 6555 Linguagem: Inglês
10.1126/science.abi7994
ISSN1095-9203
AutoresMatthew McCallum, Jessica Bassi, Anna De Marco, Alex Chen, Alexandra C. Walls, Julia di Iulio, M. Alejandra Tortorici, Mary-Jane Navarro, Chiara Silacci-Fregni, Christian Saliba, Kaitlin R. Sprouse, Maria L. Agostini, Dora Pinto, Katja Culap, Siro Bianchi, Stefano Jaconi, Elisabetta Cameroni, John E. Bowen, Sasha W. Tilles, Matteo Samuele Pizzuto, Sonja Bernasconi Guastalla, Giovanni Bona, Alessandra Franzetti-Pellanda, Christian Garzoni, Wesley C. Van Voorhis, Laura E. Rosen, Gyorgy Snell, Amalio Telenti, Herbert W. Virgin, Luca Piccoli, Davide Corti, David Veesler,
Tópico(s)vaccines and immunoinformatics approaches
ResumoA 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.
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