Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis

In this study, we used an HLA-A2 transgenic mouse model to investigate the effects of pulmonary delivery of a new DNA plasmid encoding eight HLA-A*0201-restricted T-cell epitopes from Mycobacterium tuberculosis formulated in chitosan nanoparticles. It was shown that the chitosan-DNA formulation was able to induce the maturation of dendritic cells (DCs) while chitosan solution alone could not, indicating the DNA was released from the particles and able to stimulate DCs. Pulmonary administration of the DNA plasmid incorporated in chitosan nanoparticles was shown to induce increased levels of IFN-gamma secretion compared to pulmonary delivery of plasmid in solution or the more frequently used intramuscular immunization route. These results indicate that pulmonary delivery of DNA vaccines against tuberculosis may provide an advantageous delivery route compared to intramuscular immunization, and that increased immunogenicity can be achieved by delivery of this DNA encapsulated in chitosan nanoparticles. (C) 2004 Elsevier Ltd. All rights reserved.