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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Cyrielle Fougeroux
  • Louise Goksøyr
  • Manja Idorn
  • Vladislav Soroka
  • Sebenzile K Myeni
  • Christoph M Janitzek
  • Max Søgaard
  • Emma W Horsted
  • Jerzy Dorosz
  • Stine Clemmensen
  • Laurits Fredsgaard
  • Susan Thrane
  • Elena E Vidal-Calvo
  • Paul Khalifé
  • Thomas M Hulen
  • 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
  • Tim J Dalebout
  • Lene H Harritshøj
  • Benjamin Mordmüller
  • Henrik Ullum
  • Line S Reinert
  • Willem Adriaan de Jongh
  • Marjolein Kikkert
  • Søren R Paludan

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
Issue number1
Pages (from-to)324
Publication statusPublished - 2021

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