An immunization strategy tested in mice protects against infection from SARS-CoV-2, as well as from potentially emerging animal coronaviruses, researchers say. The approach could be "used as described or easily adapted" to provide defense against newly discovered zoonotic coronaviruses. In the last 20 years, three betacoronaviruses have caused devastating disease in humans. The global pandemic caused by the latest such virus, SARS-CoV-2, highlights the need to protect against other strains that could present a threat to humans, possibly through a pan-coronavirus vaccine. To support related efforts, Alexander A. Cohen and colleagues used a "plug and display" approach to make a series of nanoparticles displaying the receptor-binding domain (RBD) of either SARS-CoV-2 alone ("homotypic nanoparticles") or the SARS-CoV-2 RBD along with a diverse set of RBDs from bat and pangolin betacoronaviruses that represent threats to humans ("mosaic nanoparticles"). In studies in mice, immunization with mosaic nanoparticles did not reduce immune response compared with immunization by a homotypic nanoparticle. What's more, mosaic nanoparticles generated cross-reactive immune responses in mice after one injection, whereas such responses required prime and boost injections in the case of the homotypic particle. The mosaic nanoparticles also elicited antibodies that, beyond recognizing the strains displayed, recognized mismatched strains, the authors say. Studying IgG antibodies from COVID-19 plasma donors, Cohen et al. found they exhibited little to no recognition of coronaviruses other than SARS-CoV-2, suggesting SARS-CoV-2-infection-induced immunity in humans would be unlikely to be protective against an outbreak of a new zoonotic coronavirus. This is yet another indication of the need to develop a vaccine to protect against emerging coronaviruses, they say. The results suggest mosaic nanoparticles as a candidate vaccine to protect against COVID-19 and other emerging coronaviruses with human spillover potential, write Cohen and team.