A self-assembled nanoparticle vaccine displaying chimeric and trimeric RBD-HRC elicits broad-spectrum neutralizing antibodies against multiple coronaviruses

Broad-spectrum vaccines are urgently needed to control the rapid evolution of viruses and their cross-species transmission. The effective presentation of epitopes, especially conserved ones, plays a critical role in vaccine design. Moreover, the polymerization of epitopes has been shown to significantly enhance immunogenicity. In this study, we present a scalable platform for developing broad-spectrum vaccines against rapidly evolving pathogens. This vaccine platform, based on self-assembling nanoparticles, displays glycosylation-modified coronavirus spike receptor-binding domain-heptad repeat C-domain (RBD-HRC) trimers, enabling the formation of multimerized and polyvalent chimeric antigens. We found that the trivalent RBD-HRC nanoparticle vaccine elicits the broadest neutralizing antibody response, strongest T-cell activation, and highest neutralization potency compared to other formulations, offering valuable insights for future vaccine development.