Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models

Science. 2022 Aug 5;377(6606):eabq0839. doi: 10.1126/science.abq0839. Epub 2022 Aug 5.

Abstract

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / immunology
  • Betacoronavirus* / immunology
  • Coronavirus Infections* / prevention & control
  • Disease Models, Animal
  • Epitopes* / chemistry
  • Epitopes* / immunology
  • Epitopes* / therapeutic use
  • Macaca
  • Mice
  • Nanoparticles* / therapeutic use
  • Protein Domains / immunology
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus* / immunology
  • Zoonoses* / prevention & control
  • Zoonoses* / virology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants