Universal broad-spectrum mucosal vaccine design for human coronaviruses inspired by artificial antibodies

Coronaviruses remain a challenge due to the limited or incomplete protection provided by existing vaccines, highlighting the need for improved antigen-based designs that can reduce mortality, block transmission, and provide long-lasting, broad-spectrum protection. In this study, we adapted artificial antibody strategies to display receptor-binding domains (RBDs) from representative human coronaviruses, utilizing an engineered human IgG1 framework modified at the Fab and Fc domains to support diverse antigen presentation and enhanced immunopotentiation. The results indicate that bivalent, tetravalent, and multivalent RBD constructs developed within this framework confer broad-spectrum immune protection against severe acute respiratory syndrome coronavirus 2 and other pathogenic coronaviruses. Moreover, Fc-mediated antigen delivery, primarily engaging the neonatal Fcγ receptor, enhances mucosal, cellular, and sustained immune responses. This underscores the versatility and practical utility of the modified IgG1 framework, based on artificial antibody strategies, for developing broad-spectrum mucosal vaccine antigens, representing promising vaccine candidates targeting human coronaviruses.