SARS-CoV-2 immune evasion by variant B.1.427/B.1.429
Autor: | David Veesler, M. Alejandra Tortorici, Davide Corti, Jessica Bassi, Alessandra Franzetti Pellanda, Matthew McCallum, Katja Culap, Wesley C. Van Voorhis, Amalio Telenti, Siro Bianchi, Christian Saliba, Julia di Iulio, Anna De Marco, Stefano Jaconi, Alexander Chen, John E. Bowen, Christian Garzoni, G. Snell, Luca Piccoli, Sonja Bernasconi Guastalla, Laura E. Rosen, Sasha W Tiles, Giovanni Bona, Matteo Samuele Pizzuto, Elisabetta Cameroni, Alexandra C. Walls, Chiara Silacci-Fregni, Dora Pinto, Herbert W. Virgin, Mary-Jane Navarro, Maria De Agostini |
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Rok vydání: | 2021 |
Předmět: |
Models
Molecular Signal peptide COVID-19 Vaccines Protein Conformation medicine.drug_class Biology Antibodies Viral Monoclonal antibody Article Neutralization Immune system Protein Domains Antigen Neutralization Tests medicine Humans Protein Interaction Domains and Motifs Antigens Viral BNT162 Vaccine Immune Evasion chemistry.chemical_classification SARS-CoV-2 Cryoelectron Microscopy Antibodies Monoclonal COVID-19 Antibodies Neutralizing Virology Protein Subunits Amino Acid Substitution chemistry Viral evolution Mutation Spike Glycoprotein Coronavirus biology.protein Antibody Glycoprotein 2019-nCoV Vaccine mRNA-1273 |
Zdroj: | bioRxiv |
Popis: | SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms. |
Databáze: | OpenAIRE |
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