title: Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.
abstract: Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB.
authors.affiliation: Molecular Microbiology Group.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukui
authors.affiliation: Molecular Microbiology Group.
authors.forename: Kikuko
authors.initials: K
authors.lastname: Shinjo
authors.affiliation: Molecular Microbiology Group.|Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Molecular Microbiology Group.
authors.forename: Satoko
authors.initials: S
authors.lastname: Shigeno
authors.affiliation: Vaccinology and Vaccine Immunology Group, Department of Infectious Diseases, Tropical Biosphere Research Center.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Harakuni
authors.affiliation: Vaccinology and Vaccine Immunology Group, Department of Infectious Diseases, Tropical Biosphere Research Center.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Molecular Microbiology Group.|Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology*; D002772:Cholera Toxin / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D020381:Interleukin-17; D037102:Lectins; C104578:heparin-binding hemagglutinin; D007371:Interferon-gamma; D002772:Cholera Toxin
keywords: IL-17A; Mycobacterium tuberculosis; heparin-binding hemagglutinin adhesion; intranasal vaccination