Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice

Fighting zoonotic coronaviruses In the past 20 years, three betacoronaviruses thought to have originated in bats have caused devastating disease in humans. The global pandemic caused by the latest such virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need to protect against other strains that could present a threat to humans. Cohen et al. constructed nanoparticles displaying the protein domain that binds the host cell receptor (receptor-binding domain or RBD), either a homotypic SARS-CoV-2 particle or mosaic particles displaying RBDs from four or eight different betacoronaviruses. In mice, antibodies to the SARS-CoV-2 RBD were elicited just as well by mosaic particles as by homotypic nanoparticles. The mosaic nanoparticles elicited antibodies that, beyond recognizing the strains displayed, also recognized mismatched strains. Science, this issue p. 735 Immunizing with nanoparticles that display diverse coronavirus receptor binding domains elicits cross-reactive and neutralizing antibody responses. Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles with four to eight distinct RBDs). Mice immunized with RBD nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic RBD nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs relative to sera from immunizations with homotypic SARS-CoV-2–RBD nanoparticles or COVID-19 convalescent human plasmas. Moreover, after priming, sera from mosaic RBD–immunized mice neutralized heterologous pseudotyped coronaviruses as well as or better than sera from homotypic SARS-CoV-2–RBD nanoparticle immunizations, demonstrating no loss of immunogenicity against particular RBDs resulting from co-display. A single immunization with mosaic RBD nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.

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