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

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Existing coronavirus vaccines offer limited protection, necessitating improved antigen designs.
• There is a critical need for vaccines that reduce mortality, block transmission, and provide long-lasting, broad-spectrum immunity against coronaviruses.

Purpose of the Study:

• To develop novel vaccine antigen strategies using artificial antibodies for enhanced coronavirus protection.
• To engineer an IgG1 framework for diverse antigen presentation and improved immunopotentiation.

Main Methods:

• Artificial antibody strategies were employed to display receptor-binding domains (RBDs) from human coronaviruses.
• An engineered human IgG1 framework was modified at Fab and Fc domains for antigen display and immune enhancement.
• Bivalent, tetravalent, and multivalent RBD constructs were generated.

Main Results:

• RBD constructs demonstrated broad-spectrum immune protection against SARS-CoV-2 and other pathogenic coronaviruses.
• Fc-mediated antigen delivery, via the neonatal Fcγ receptor, enhanced mucosal, cellular, and sustained immune responses.
• The engineered IgG1 framework proved versatile for presenting diverse antigens.

Conclusions:

• Modified IgG1 framework using artificial antibody strategies is effective for developing broad-spectrum mucosal vaccine antigens.
• These constructs represent promising vaccine candidates for targeting human coronaviruses.
• The approach enhances immune responses, offering a potential solution to current vaccine limitations.