Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.
Alexander A CohenNeeltje Van DoremalenAllison J GreaneyHanne A ElyardAnkur SharmaTyler N StarrJennifer R KeeffeChengcheng FanJonathan E SchulzPriyanthi N P GnanapragasamLeesa M KakutaniAnthony P WestGreg SaturdayYu Erica LeeHan GaoClaudia A JetteMark G LewisTiong Kit TanAlain R TownsendJesse D BloomVincent J MunsterPamela J BjorkmanPublished in: Science (New York, N.Y.) (2022)
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.