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 Erdogan, Tobias Gustavsson, Jerzy Dorosz, Stine Clemmensen, Laurits Fredsgaard, Susan Thrane, Elena E Vidal-Calvo, Paul Khalifé, Thomas M Hulen, Swati ChoudharyMichael Theisen, Susheel K Singh, Asier Garcia-Senosiain, Linda Van 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 de Jongh, Marjolein Kikkert, Søren R Paludan, Thor G Theander, Morten A Nielsen, Ali Salanti, Adam F Sander

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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.

Original languageEnglish
JournalNature Communications
Volume12
Issue number1
Pages (from-to)324
ISSN2041-1723
DOIs
Publication statusPublished - 2021

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