Enhanced mucosal immune response through nanoparticle delivery system based on chitosan-catechol and a recombinant antigen targeted towards M cells.

In mucosal vaccination, the targeted delivery of antigens through M (microfold) cells is essential for initiating a robust antigen-specific immune response. In the present study, we devised a nano-delivery platform to target M cells. This platform involved coating mesoporous silica nanoparticles (MSN) with a mucoadhesive chitosan-catechol (Chic) layer, incorporating a recombinant antigen to form nanoparticles that enhance the immune response. The collagenase equivalent domain (COE) of porcine epidemic diarrhea virus (PEDV) terminated with the M cell-targeting sequence RGD (COER), was initially expressed by Escherichia coli (E. coli) and subsequently conjugated to the surface of MSN-Chic, forming the MSN-Chic-COER nanoparticles. MSN-Chic-COER with strong mucoadhesive properties and a propensity for M cell targeting, demonstrated enhanced uptake by dendritic cells (DCs) and trafficking to lymph nodes, compared to COE/COER after intranasal administration. MSN-Chic-COER recruited more dendritic cells to the antigen-located site via stimulating chemokine CCL20 secretion was evidenced by cell co-culture model. Additionally, it enhanced antigen permeability by disrupting the distribution of the ZO-1 protein in epithelial cells. Notably, MSN-Chic-COER elicited a higher level of cellular immunity, humoral immunity, and PEDV neutralizing antibody production. These findings underscore the potential of MSN-Chic-COER as a promising intranasal vaccine delivery system.