Oral DNA Vaccine Utilizing the Yeast Cell Wall for Dectin-1 Receptor-Mediated Enhancement of Mucosal Immunity

Mucosal vaccines can generate localized mucosal immunity, effectively preventing initial pathogen infection and providing more effective protection. Oral vaccines are an attractive option for inducing mucosal immunity. The yeast cell wall, primarily composed of natural β-1,3-d glucan, can be recognized by the apical membrane receptor, dectin-1, which has a high expression on macrophages and intestinal M cells. In this study, by using vortexing methods to break yeast cell walls into nanometer-sized fragments, which retain the negatively charged β-glucan components on their surface and employing electrostatic adsorption/coextrusion techniques, these fragments were attached onto the surface of PS-DNA NPs, as verified by a scanning electron microscope (SEM), a transmission electron microscope (TEM), and dynamic light scattering (DLS) data. YCW-coated NPs (YNPs) showed greater drug stability compared to NPs in a simulated gastrointestinal environment. In vitro cell evaluation further demonstrated that YNPs were rapidly and efficiently taken up by antigen-presenting cells via receptor dectin-1-mediated endocytosis. In vivo experiments revealed that the oral vaccine elicited high levels of RBD-specific antibodies and triggered extensive cellular immunity in the intestinal mucosa. This study provides new insights into mucosal vaccine research.