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

TLDR

Urgent need exists to protect against SARS‑CoV‑2 and related zoonotic coronaviruses. The authors engineered homotypic and mosaic nanoparticles that display the SARS‑CoV‑2 receptor‑binding domain alone or together with RBDs from animal betacoronaviruses, creating multivalent antigen displays. Mice immunized with mosaic RBD nanoparticles produced cross‑reactive binding and neutralization against diverse coronaviruses, outperforming homotypic RBD nanoparticles and convalescent human plasma, and a single dose conferred broad protection.

Abstract

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.