title: Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice.
abstract: It is generally accepted that cellular immunity plays a critical role in the protection against Mycobacterium tuberculosis, an intracellular pathogen. Recently, however, an increasing number of reports indicate the important contribution of humoral immunity against mycobacterial infection. Since M. tuberculosis establishes its primary lesion in the lung, induction of humoral immunity in the airway tract by mucosal immunization regime could provide protective immunity against tuberculosis. In this study, mycobacterial heparin-binding haemagglutinin adhesin (HBHA) was used as an immunization antigen because HBHA is an essential virulence factor required for the infection of lung epithelial cells and extrapulmonary dissemination of mycobacteria. The effects of intranasal immunization with a yeast-expressed recombinant (r) HBHA co-administered with a mucosal adjuvant cholera toxin (CT) on the induction of humoral and cellular immunity were examined, and its protective efficacy against pulmonary challenge infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) was evaluated. HBHA-specific antibodies were induced in serum and airway tract of immunized mice, which specifically recognized native HBHA expressed on M. bovis BCG. Th1-type immunity against mycobacterial antigens was also enhanced in the lung of immunized mice after pulmonary BCG infection. Furthermore, the immunization suppressed bacterial load in the spleen after pulmonary BCG infection. These results indicate that systemic and local humoral immunity induced by the HBHA-based mucosal vaccine impairs extrapulmonary dissemination, thus providing immune protection against mycobacterial infection.
authors.affiliation: Molecular Microbiology Group, Center of Molecular Biosciences, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kohama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Ayano
authors.initials: A
authors.lastname: Yahagi
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Goga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Harakuni
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D006388:Hemagglutinins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D007114:Immunization; D037102:Lectins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D006388:Hemagglutinins; D037102:Lectins; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines; C104578:heparin-binding hemagglutinin; D002772:Cholera Toxin