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Article Dans Une Revue Nature Année : 2023

Neutralization, effector function and immune imprinting of Omicron variants

Luca Piccoli
Young-Jun Park
Barbara Guarino
  • Fonction : Auteur
Dora Pinto
  • Fonction : Auteur
Kaitlin Sprouse
Jessica Bassi
Francesco Muoio
Marco Dini
Christian Saliba
Gloria Lombardo
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Giada Leoni
  • Fonction : Auteur
Katja Culap
Anushka Rajesh
Exequiel Dellota
Jiayi Zhou
Dana Bohan
Alex Chen
Florian Lempp
Laura Rosen
Fabio Benigni
  • Fonction : Auteur
Nicholas Franko
Jennifer Logue
Cameron Stewart
Helen Chu
Michael Schmid
Lisa Purcell
Gyorgy Snell
Davide Corti
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Résumé

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (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.
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Origine : Publication financée par une institution
Licence : CC BY - Paternité

Dates et versions

hal-04240898 , version 1 (19-10-2023)

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Paternité

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Amin Addetia, Luca Piccoli, James Brett Case, Young-Jun Park, Martina Beltramello, et al.. Neutralization, effector function and immune imprinting of Omicron variants. Nature, 2023, 621 (7979), pp.592-601. ⟨10.1038/s41586-023-06487-6⟩. ⟨hal-04240898⟩

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