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Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

Author

Listed:
  • Cyrielle Fougeroux

    (AdaptVac Aps)

  • Louise Goksøyr

    (AdaptVac Aps
    Copenhagen University Hospital)

  • Manja Idorn

    (Aarhus University)

  • Vladislav Soroka

    (ExpreS2ion Biotechnologies Aps)

  • Sebenzile K. Myeni

    (Leiden University Medical Center)

  • Robert Dagil

    (Copenhagen University Hospital
    VAR2pharmaceuticals)

  • Christoph M. Janitzek

    (Copenhagen University Hospital)

  • Max Søgaard

    (ExpreS2ion Biotechnologies Aps)

  • Kara-Lee Aves

    (Copenhagen University Hospital)

  • Emma W. Horsted

    (Copenhagen University Hospital)

  • Sayit Mahmut Erdoğan

    (Copenhagen University Hospital
    Turkish Ministry of Agriculture and Forestry)

  • Tobias Gustavsson

    (Copenhagen University Hospital
    VAR2pharmaceuticals)

  • Jerzy Dorosz

    (ExpreS2ion Biotechnologies Aps)

  • Stine Clemmensen

    (ExpreS2ion Biotechnologies Aps)

  • Laurits Fredsgaard

    (Copenhagen University Hospital)

  • Susan Thrane

    (AdaptVac Aps)

  • Elena E. Vidal-Calvo

    (VAR2pharmaceuticals)

  • Paul Khalifé

    (Copenhagen University Hospital)

  • Thomas M. Hulen

    (Copenhagen University Hospital)

  • Swati Choudhary

    (Copenhagen University Hospital
    VAR2pharmaceuticals)

  • Michael Theisen

    (Copenhagen University Hospital
    Statens Serum Institute)

  • Susheel K. Singh

    (Copenhagen University Hospital
    Statens Serum Institute)

  • Asier Garcia-Senosiain

    (Copenhagen University Hospital
    Statens Serum Institute)

  • Linda Oosten

    (Laboratory of Virology)

  • Gorben Pijlman

    (Laboratory of Virology)

  • Bettina Hierzberger

    (ExpreS2ion Biotechnologies Aps)

  • Tanja Domeyer

    (ExpreS2ion Biotechnologies Aps)

  • Blanka W. Nalewajek

    (ExpreS2ion Biotechnologies Aps)

  • Anette Strøbæk

    (ExpreS2ion Biotechnologies Aps)

  • Magdalena Skrzypczak

    (ExpreS2ion Biotechnologies Aps)

  • Laura F. Andersson

    (ExpreS2ion Biotechnologies Aps)

  • Søren Buus

    (University of Copenhagen)

  • Anette Stryhn Buus

    (University of Copenhagen)

  • Jan Pravsgaard Christensen

    (University of Copenhagen)

  • Tim J. Dalebout

    (Leiden University Medical Center)

  • Kasper Iversen

    (Herlev Hospital)

  • Lene H. Harritshøj

    (Copenhagen University Hospital)

  • Benjamin Mordmüller

    (Universitätsklinikum Tübingen, Institut für Tropenmedizin
    Centre de Recherches Médicales de Lambaréné)

  • Henrik Ullum

    (Herlev Hospital)

  • Line S. Reinert

    (Aarhus University)

  • Willem Adriaan Jongh

    (AdaptVac Aps
    ExpreS2ion Biotechnologies Aps)

  • Marjolein Kikkert

    (Leiden University Medical Center)

  • Søren R. Paludan

    (Aarhus University)

  • Thor G. Theander

    (Copenhagen University Hospital)

  • Morten A. Nielsen

    (Copenhagen University Hospital)

  • Ali Salanti

    (Copenhagen University Hospital
    VAR2pharmaceuticals)

  • Adam F. Sander

    (AdaptVac Aps
    Copenhagen University Hospital)

Abstract

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.

Suggested Citation

  • Cyrielle Fougeroux & Louise Goksøyr & Manja Idorn & Vladislav Soroka & Sebenzile K. Myeni & Robert Dagil & Christoph M. Janitzek & Max Søgaard & Kara-Lee Aves & Emma W. Horsted & Sayit Mahmut Erdoğan , 2021. "Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20251-8
    DOI: 10.1038/s41467-020-20251-8
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    Cited by:

    1. Susan K. Vester & Rolle Rahikainen & Irsyad N. A. Khairil Anuar & Rory A. Hills & Tiong Kit Tan & Mark Howarth, 2022. "SpySwitch enables pH- or heat-responsive capture and release for plug-and-display nanoassembly," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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