Virus like nanoparticles of VLP-BSA-iRGD enhanced mucosal immune response by targeting M cells

In mucosal immunity, targeting microfolds (M)cells of the mucosal epithelium, in combination with suitable adjuvants, is critical for eliciting robust immune response. In the present study, we devised a virus like nanoparticles (VLP)-based nano-delivery platform functionalized with the M cell-targeting peptide iRGD (RGDKGPDC) to enhance the immune responses following intranasal administration. Bovine serum albumin (BSA) was selected as a model antigen, and both BSA and iRGD were conjugated to the VLP surface, forming VLP-BSA-iRGD nanoparticles. Leveraging its M cell-targeting capability, VLP-BSA-iRGD demonstrated enhanced uptake by dendritic cells (DCs) and improved trafficking to lymph nodes compared to BSA alone in a mouse model. VLP-BSA-iRGD enhanced the CCL20 secretion and stimulated the DC activation, as evidenced by an in vitro cell co-culture model. Additionally, it enhanced antigen permeability by disrupting the distribution of the ZO-1 protein in epithelial cells. Importantly, VLP-BSA-iRGD induced stronger humoral and cellular immune responses, accompanied by the upregulation of TLR2/4 expression and activation of the MYD88/NF-κB signaling pathway in DCs. While BSA served as a proof-of-concept antigen, this platform may be broadly applicable to other protein-based subunit vaccines requiring intranasal administration.