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

Nat Commun. 2021 Jan 12;12(1):324. doi: 10.1038/s41467-020-20251-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines / immunology*
  • Capsid / immunology*
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding / genetics
  • Protein Binding / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • SARS-CoV-2 / immunology*
  • Serologic Tests
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2