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  • Mosaic RBD nanoparticles pr...
    Cohen, Alexander A; van Doremalen, Neeltje; Greaney, Allison J; Andersen, Hanne; Sharma, Ankur; Starr, Tyler N; Keeffe, Jennifer R; Fan, Chengcheng; Schulz, Jonathan E; Gnanapragasam, Priyanthi N P; Kakutani, Leesa M; West, Jr, Anthony P; Saturday, Greg; Lee, Yu E; Gao, Han; Jette, Claudia A; Lewis, Mark G; Tan, Tiong K; Townsend, Alain R; Bloom, Jesse D; Munster, Vincent J; Bjorkman, Pamela J

    Science (American Association for the Advancement of Science), 08/2022, Volume: 377, Issue: 6606
    Journal Article

    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.