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

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, Tobias Gustavsson, Jerzy Dorosz, Stine Clemmensen, Laurits Fredsgaard, Susan Thrane, Elena E. Vidal-Calvo, Paul Khalifé, Thomas M. Hulen, Swati Choudhary, Michael Theisen, Susheel K. Singh, Asier Garcia-Senosiain, Linda Oosten, Gorben Pijlman, Bettina Hierzberger, Tanja Domeyer, Blanka W. Nalewajek, Anette Strøbæk, Magdalena Skrzypczak, Laura F. Andersson, Søren Buus, Anette Stryhn Buus, Jan Pravsgaard Christensen, Tim J. Dalebout, Kasper Iversen, Lene H. Harritshøj, Benjamin Mordmüller, Henrik Ullum, Line S. Reinert, Willem Adriaan Jongh, Marjolein Kikkert, Søren R. Paludan, Thor G. Theander, Morten A. Nielsen (), Ali Salanti and Adam F. Sander ()
Additional contact information
Cyrielle Fougeroux: AdaptVac Aps
Louise Goksøyr: AdaptVac Aps
Manja Idorn: Aarhus University
Vladislav Soroka: ExpreS2ion Biotechnologies Aps
Sebenzile K. Myeni: Leiden University Medical Center
Robert Dagil: Copenhagen University Hospital
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
Tobias Gustavsson: Copenhagen University Hospital
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
Michael Theisen: Copenhagen University Hospital
Susheel K. Singh: Copenhagen University Hospital
Asier Garcia-Senosiain: Copenhagen University Hospital
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
Henrik Ullum: Herlev Hospital
Line S. Reinert: Aarhus University
Willem Adriaan Jongh: AdaptVac 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
Adam F. Sander: AdaptVac Aps

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20251-8

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