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174 2 RBD along with diverse RBDs on mosaic nanoparticles showed no disadvantages for eliciting

neutralizing antibodies against SARS-CoV-2 compared with homotypic SARS-2 nanoparticles, sug- gesting mosaic nanoparticles as a candidate vaccine to protect against COVID-19. Furthermore, compared with homotypic SARS-2 RBD particles, the mosaic co-display strategy demonstrated ad- vantages for eliciting neutralizing antibodies against zoonotic sarbecoviruses, thus potentially also providing protection against emerging coronaviruses with human spillover potential. Neutralization of matched and mismatched strains was observed after mosaic priming, suggesting a single injec- tion of a mosaic-RBD nanoparticle might be sufficient in a vaccine. Since COVID-19 convalescent plasmas showed little to no recognition of coronavirus RBDs other than SARS-CoV-2, COVD-19–

induced immunity in humans may not protect against another emergent coronavirus. However, the mosaic nanoparticles described here could be used as described or easily adapted to present RBDs from newly-discovered zoonotic coronaviruses.

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Acknowledgements

We thank Karl Brune (Genie Biotech) for advice about mi3 production, Jesse Bloom (Fred Hutchinson) and Paul Bieniasz (Rockefeller University) for neutralization assay reagents, Jost

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