title: Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, PO Box 9502, 2300 RA Leiden, The Netherlands. m.bivas@lacdr.leidenuniv.nl
authors.forename: Maytal
authors.initials: M
authors.lastname: Bivas-Benita
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Hans E
authors.initials: HE
authors.lastname: Junginger
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002686:Chitin / Q000031:analogs & derivatives*; D048271:Chitosan; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics*; D005079:Excipients; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D000939:Epitopes; D005079:Excipients; D015234:HLA-A Antigens; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D002686:Chitin; D007371:Interferon-gamma; D048271:Chitosan