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

## TL;DR

This paper introduces a new mucosal vaccine design using artificial antibodies to provide broad protection against multiple human coronaviruses.

## Contribution

The novel use of an engineered IgG1 framework to display multiple coronavirus RBDs for broad-spectrum mucosal vaccine development.

## Key findings

- Bivalent, tetravalent, and multivalent RBD constructs confer broad immune protection against SARS-CoV-2 and other coronaviruses.
- Fc-mediated antigen delivery enhances mucosal and sustained immune responses via the neonatal Fcγ receptor.

## Abstract

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.