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

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…

• BA
  Bill and Melinda Gates Foundation

  Awards: INV-034638, INV-004949, INV-016575
• DR
  Damon Runyon Cancer Research Foundation

  Award: DRG-2381-19
• FH
  Fred Hutchinson Cancer Research Center
• GM
  George Mason University
• CI
  California Institute of Technology
• UO
  University of Washington
• PH
  Public Health Agency of Canada
• PH
  Public Health Agency
• NI
  National Institutes of Health

  Awards: HHSN272201400006C, S10OD028685, 1ZIAAI001179-01, 75N93021C00015, P40 OD012217, R01AI141707
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: 1ZIAAI001179-01, R01AI141707, HHSN272201400006C, 75N93021C00015
• OO
  Office of Research Infrastructure Programs, National Institutes of Health

  Awards: S10OD028685, P40 OD012217