Neutralization, effector function and immune imprinting of Omicron variants

Addetia, Amin and Piccoli, Luca and Case, James Brett and Park, Young-Jun and Beltramello, Martina and Guarino, Barbara and Dang, Ha and de Melo, Guilherme Dias and Pinto, Dora and Sprouse, Kaitlin and Scheaffer, Suzanne M. and Bassi, Jessica and Silacci-Fregni, Chiara and Muoio, Francesco and Dini, Marco and Vincenzetti, Lucia and Acosta, Rima and Johnson, Daisy and Subramanian, Sambhavi and Saliba, Christian and Giurdanella, Martina and Lombardo, Gloria and Leoni, Giada and Culap, Katja and McAlister, Carley and Rajesh, Anushka and Dellota, Exequiel and Zhou, Jiayi and Farhat, Nisar and Bohan, Dana and Noack, Julia and Chen, Alex and Lempp, Florian A. and Quispe, Joel and Kergoat, Lauriane and Larrous, Florence and Cameroni, Elisabetta and Whitener, Bradley and Giannini, Olivier and Cippà, Pietro and Ceschi, Alessandro and Ferrari, Paolo and Franzetti-Pellanda, Alessandra and Biggiogero, Maira and Garzoni, Christian and Zappi, Stephanie and Bernasconi, Luca and Kim, Min Jeong and Rosen, Laura E. and Schnell, Gretja and Czudnochowski, Nadine and Benigni, Fabio and Franko, Nicholas and Logue, Jennifer K. and Yoshiyama, Courtney and Stewart, Cameron and Chu, Helen and Bourhy, Hervé and Schmid, Michael A. and Purcell, Lisa A. and Snell, Gyorgy and Lanzavecchia, Antonio and Diamond, Michael S. and Corti, Davide and Veesler, David (2023) Neutralization, effector function and immune imprinting of Omicron variants. Nature, 621 (7979). pp. 592-601. ISSN 0028-0836

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Abstract

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

Item Type: Article
Subjects: Pustakas > Multidisciplinary
Depositing User: Unnamed user with email support@pustakas.com
Date Deposited: 14 Nov 2023 07:40
Last Modified: 14 Nov 2023 07:40
URI: http://archive.pcbmb.org/id/eprint/1498

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