Dual-targeting oral nanoparticle mucosal vaccine against brucella infection: co-targeting M cells and dendritic cells.

This study designed and evaluated a chitosan nanoparticle-based mucosal vaccine (CS-CKS9-MEV-DCpep-NPs) targeting M cells and dendritic cells against Brucella. From four immunogenic outer membrane proteins (OMP10, Omp25, Omp31, BtpB), 41 specific epitope peptides were screened and optimized via bioinformatics and ELISPOT for high antigenicity and safety. The dual-targeting strategy uses CKS9 to enhance M cell-mediated antigen uptake and DCpep, together with CS-NPs, to activate DCs and promote their maturation. This coordinates cDC1, cDC2, and pDC subsets, inducing CD8⁺ and CD4⁺ T cell responses and strengthening Th1-biased immunity against intracellular bacteria. The vaccine activates mucosal (sIgA), humoral (IL-21, memory B cells), and cellular (Th1/CTL, central memory T cells) immunity. It significantly reduces bacterial load and tissue damage, offering comprehensive protection. Compared with conventional vaccines, this oral nanovaccine provides high safety, precise targeting, and multi-dimensional immune activation, representing a novel strategy for brucellosis control.