title: Enhanced protection against pulmonary mycobacterial challenge by chitosan-formulated polyepitope gene vaccine is associated with increased pulmonary secretory IgA and gamma-interferon(+) T cell responses.
abstract: Induction of local (pulmonary) immunity plays a critical role in preventing dissemination of Mycobacterium tuberculosis (M. tb) during the early infection stage. To induce specific mucosal immunity, chitosan, a natural cationic polysaccharide, was employed as a mucosal gene carrier and complexed with pHSP65pep, our previously constructed multi-epitope gene vaccine, which induces splenic gamma-interferon (IFN-γ)(+) T helper cell 1 responses. The resultant chitosan-pHSP65pep was administered intranasally to BALB/c mice with four doses of 50 μg DNA followed by mycobacterial challenge 4 weeks after the final immunization. It was found that the chitosan formulation significantly induced production of secretory immunoglobulin A (P < 0.05) as determined by measuring its concentrations in lung lavage fluid and enhanced pulmonary CD4(+) and CD8(+) IFN-γ(+) T cell responses (P < 0.001) compared with naked gene vaccine. Improved protection against Mycobacterium bovis bacillus Calmette-Guérin (BCG) challenge was consistently achieved by the chitosan-DNA formulation both as the vaccine alone or in a BCG prime-vaccine boost immunization scenario. Our study shows that mucosal delivery of gene vaccine in a chitosan formulation remarkably enhances specific SIgA concentrations and mucosal IFN-γ(+) T cell response, which correlated positively with immunological protection.
authors.affiliation: Institute for Immunobiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Ai
authors.forename: Yan
authors.initials: Y
authors.lastname: Yue
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D048271:Chitosan / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D004337:Drug Carriers; D000939:Epitopes; D007071:Immunoglobulin A, Secretory; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D048271:Chitosan