Universal broad-spectrum mucosal vaccine design for human coronaviruses inspired by artificial antibodies
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The continued challenge posed by coronaviruses is largely due to the limited or incomplete protection provided by existing vaccines, highlighting the need for effective antigen-based designs capable of yielding optimal vaccines that reduce mortality, block transmission, and provide long-term broad-spectrum protection. In the current study, we adapted artificial antibody strategies to display receptor-binding domains (RBDs) from representative human coronaviruses using 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 (SARS-CoV-2) and other pathogenic coronaviruses. Moreover, Fc-mediated antigen delivery, primarily engaging the neonatal Fcγ receptor, enhances mucosal, cellular, and long-term immune responses. This highlights the versatility and practical value of the modified IgG1 framework, based on artificial antibody strategies, for developing broad-spectrum mucosal vaccine antigens, and presents promising vaccine candidates targeting human coronaviruses.
