Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice

FEBS Lett. 2021 Sep;595(18):2323-2340. doi: 10.1002/1873-3468.14171. Epub 2021 Aug 22.


The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has triggered a worldwide health emergency. Here, we show that ferritin-like Dps from hyperthermophilic Sulfolobus islandicus, covalently coupled with SARS-CoV-2 antigens via the SpyCatcher system, forms stable multivalent dodecameric vaccine nanoparticles that remain intact even after lyophilisation. Immunisation experiments in mice demonstrated that the SARS-CoV-2 receptor binding domain (RBD) coupled to Dps (RBD-S-Dps) elicited a higher antibody titre and an enhanced neutralising antibody response compared to monomeric RBD. A single immunisation with RBD-S-Dps completely protected hACE2-expressing mice from serious illness and led to viral clearance from the lungs upon SARS-CoV-2 infection. Our data highlight that multimerised SARS-CoV-2 subunit vaccines are a highly efficacious modality, particularly when combined with an ultra-stable scaffold.

Keywords: COVID-19; Dps; RBD; SARS-CoV-2; coronavirus; subunit vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / immunology*
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Bacterial Proteins / chemistry
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / chemistry
  • COVID-19 Vaccines / immunology*
  • DNA-Binding Proteins / chemistry
  • Ferritins / chemistry
  • Humans
  • Immunization
  • Mice
  • Nanoparticles
  • Protein Domains
  • Protein Multimerization
  • Receptors, Virus / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Sulfolobus


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Bacterial Proteins
  • COVID-19 Vaccines
  • DNA-Binding Proteins
  • DPS protein, Bacteria
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Ferritins
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Associated data

  • RefSeq/AGJ61963.1
  • RefSeq/MN908947
  • RefSeq/MW041156