IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v621y2023i7979d10.1038_s41586-023-06487-6.html
   My bibliography  Save this article

Neutralization, effector function and immune imprinting of Omicron variants

Author

Listed:
  • Amin Addetia

    (University of Washington)

  • Luca Piccoli

    (Humabs BioMed)

  • James Brett Case

    (Washington University School of Medicine)

  • Young-Jun Park

    (University of Washington)

  • Martina Beltramello

    (Humabs BioMed)

  • Barbara Guarino

    (Humabs BioMed)

  • Ha Dang

    (Vir Biotechnology)

  • Guilherme Dias de Melo

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Dora Pinto

    (Humabs BioMed)

  • Kaitlin Sprouse

    (University of Washington)

  • Suzanne M. Scheaffer

    (Washington University School of Medicine)

  • Jessica Bassi

    (Humabs BioMed)

  • Chiara Silacci-Fregni

    (Humabs BioMed)

  • Francesco Muoio

    (Humabs BioMed)

  • Marco Dini

    (Humabs BioMed)

  • Lucia Vincenzetti

    (Humabs BioMed)

  • Rima Acosta

    (Vir Biotechnology)

  • Daisy Johnson

    (Vir Biotechnology)

  • Sambhavi Subramanian

    (Vir Biotechnology)

  • Christian Saliba

    (Humabs BioMed)

  • Martina Giurdanella

    (Humabs BioMed)

  • Gloria Lombardo

    (Humabs BioMed)

  • Giada Leoni

    (Humabs BioMed)

  • Katja Culap

    (Humabs BioMed)

  • Carley McAlister

    (Vir Biotechnology)

  • Anushka Rajesh

    (Vir Biotechnology)

  • Exequiel Dellota

    (Vir Biotechnology)

  • Jiayi Zhou

    (Vir Biotechnology)

  • Nisar Farhat

    (Vir Biotechnology)

  • Dana Bohan

    (Vir Biotechnology)

  • Julia Noack

    (Vir Biotechnology)

  • Alex Chen

    (Vir Biotechnology)

  • Florian A. Lempp

    (Vir Biotechnology)

  • Joel Quispe

    (University of Washington)

  • Lauriane Kergoat

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Florence Larrous

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Elisabetta Cameroni

    (Humabs BioMed)

  • Bradley Whitener

    (Washington University School of Medicine)

  • Olivier Giannini

    (Università della Svizzera italiana
    Ente Ospedaliero Cantonale)

  • Pietro Cippà

    (Università della Svizzera italiana
    Ente Ospedaliero Cantonale
    Ente Ospedaliero Cantonale)

  • Alessandro Ceschi

    (Università della Svizzera italiana
    Ente Ospedaliero Cantonale
    Ente Ospedaliero Cantonale
    University Hospital Zurich)

  • Paolo Ferrari

    (Università della Svizzera italiana
    Ente Ospedaliero Cantonale
    University of New South Wales)

  • Alessandra Franzetti-Pellanda

    (Clinica Luganese Moncucco)

  • Maira Biggiogero

    (Clinica Luganese Moncucco)

  • Christian Garzoni

    (Clinica Luganese Moncucco)

  • Stephanie Zappi

    (Cantonal Hospital Aarau)

  • Luca Bernasconi

    (Cantonal Hospital Aarau)

  • Min Jeong Kim

    (Cantonal Hospital Aarau)

  • Laura E. Rosen

    (Vir Biotechnology)

  • Gretja Schnell

    (Vir Biotechnology)

  • Nadine Czudnochowski

    (Vir Biotechnology)

  • Fabio Benigni

    (Humabs BioMed)

  • Nicholas Franko

    (University of Washington)

  • Jennifer K. Logue

    (University of Washington)

  • Courtney Yoshiyama

    (University of Washington)

  • Cameron Stewart

    (University of Washington)

  • Helen Chu

    (University of Washington)

  • Hervé Bourhy

    (Université Paris Cité, Lyssavirus Epidemiology and Neuropathology Unit)

  • Michael A. Schmid

    (Humabs BioMed)

  • Lisa A. Purcell

    (Vir Biotechnology)

  • Gyorgy Snell

    (Vir Biotechnology)

  • Antonio Lanzavecchia

    (Humabs BioMed)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Davide Corti

    (Humabs BioMed)

  • David Veesler

    (University of Washington
    University of Washington)

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.

Suggested Citation

  • Amin Addetia & Luca Piccoli & James Brett Case & Young-Jun Park & Martina Beltramello & Barbara Guarino & Ha Dang & Guilherme Dias de Melo & Dora Pinto & Kaitlin Sprouse & Suzanne M. Scheaffer & Jessi, 2023. "Neutralization, effector function and immune imprinting of Omicron variants," Nature, Nature, vol. 621(7979), pages 592-601, September.
  • Handle: RePEc:nat:nature:v:621:y:2023:i:7979:d:10.1038_s41586-023-06487-6
    DOI: 10.1038/s41586-023-06487-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-023-06487-6
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-023-06487-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Deborah Cromer & Arnold Reynaldi & Ainslie Mitchell & Timothy E. Schlub & Jennifer A. Juno & Adam K. Wheatley & Stephen J. Kent & David S. Khoury & Miles P. Davenport, 2024. "Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    3. Delphine Planas & Isabelle Staropoli & Vincent Michel & Frederic Lemoine & Flora Donati & Matthieu Prot & Francoise Porrot & Florence Guivel-Benhassine & Banujaa Jeyarajah & Angela Brisebarre & Océane, 2024. "Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:621:y:2023:i:7979:d:10.1038_s41586-023-06487-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.