title: Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity.
abstract: We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting of the mucosal adjuvant LTK63 and the Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette-Guérin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A. Because a crucial element of novel vaccine strategies is the ability to boost BCG-derived immunity, we also tested whether LTK63/Ag85B-ESAT-6 could act as a BCG booster vaccine in BCG-vaccinated mice. We found that vaccinating with LTK63/Ag85B-ESAT-6 strongly boosted prior BCG-stimulated immunity. Compared with BCG-vaccinated nonboosted mice, we observed that infection with M.tb led to a significant increase in anti-M.tb-specific CD4 T cells in the lungs of LTK63/Ag85B-ESAT-6-boosted animals. This correlated with a significant increase in the protection against M.tb in LTK63/Ag85B-ESAT-6-boosted mice, compared with BCG-vaccinated animals. Thus, LTK63/Ag85B-ESAT-6 represents an efficient preventive vaccine against tuberculosis with a strong ability to boost prior BCG immunity.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institute, Artillerivej 5, DK-2300 Copenhagen, Denmark. JDI@ssi.dk
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.forename: Claire
authors.initials: C
authors.lastname: Andersen
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Charlotte Green
authors.initials: CG
authors.lastname: Jensen
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage* / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000276:immunology; D007117:Immunization, Secondary; D051379:Mice; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis; D009297:Nasal Mucosa / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; C027538:heat-labile enterotoxin, E coli; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis