In vitro and in vivo investigation of chitosan–polylysine polymeric nanoparticles for ovalbumin and CpG co-delivery

Abstract

In this work, a simple and powerful vaccine delivery system was developed by the electrostatic binding of chitosan-based polycation methoxy poly(ethylene glycol)–chitosan–poly(L-lysine) (mPEG–CS–PLL) with ovalbumin (OVA) and unmethylated cytosine–phosphate–guanine (CpG). OVA was used as the model antigen and co-loaded with the adjuvant CpG in the nanoparticles (NPs) to increase the vaccine efficacy. This vaccine delivery system could induce enhanced immune responses by simultaneously delivering the immunostimulating adjuvant CpG with OVA antigen. The vaccine delivery system was found to promote the cell uptake of antigens into bone-marrow-derived dendritic cells (BMDCs). Moreover, the OVA and CpG co-loaded NPs showed much higher efficiency to stimulate BMDCs maturation and proinflammatory cytokine secretion compared with OVA alone and the OVA-loaded NPs. The cell viability assay in BMDCs verified that the chitosan-based NPs didn't hamper the cell viabilities. Finally, the OVA and CpG co-loaded NPs were confirmed to induce improved OVA-specific antibody production and increased IFN-γ producing T cells, suggesting that this simple vaccine delivery system had the ability to powerfully induce both humoral and cellular immune responses. This study clearly demonstrated that the chitosan-based NPs had great promise to be applied in vaccine delivery for the treatment of infectious diseases and cancers in the future.