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. Graphical