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.
【초록키워드】 SARS-CoV-2, coronavirus, immune response, antibody, SARS-CoV, neutralization, variant, SARS-CoV-2 variant, immunization, Health, SARS-CoV-2 variants, mice, RBD, response, spike receptor-binding domain, macaque, epitope, Strains, Sarbecoviruses, sarbecovirus, RBDs, acute respiratory syndrome, immunodominant, Randomly, Seven, PROTECT, conserved, demonstrated, elicit, elicited, betacoronavirus, 【제목키워드】 animal model, RBD, mosaic, PROTECT, sarbecovirus,