title: Strain-specific pulmonary defense achieved after repeated airway immunizations with non-typeable haemophilus influenzae in a mouse model.
abstract: Strain-specific immune responses may play a critical role in the acute exacerbation of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of surface antigens of NTHi, which may contribute to the strain-specific protective immunity. We examined whether repeated airway immunizations with killed-NTHi strains bearing different P2 molecules were capable of inducing protective immunity against homologous or heterologous strains in the lungs of a mouse model. Three different strains of NTHi were used in this study. Three serial intratracheal (IT) immunizations of a single strain or three different strains of NTHi led to the production of cross-reactive immunoglobulins G and A in bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain enhanced the bacterial clearance of the homologous strain in the lungs, but no enhancement of bacterial clearance was found with three serial IT immunizations of heterologous strains. The enhancement in bacterial clearance, therefore, appears to be primarily strain-specific. Enhanced bacterial clearance of a heterologous strain was also found after three serial IT immunizations of a single strain among two of the three strains employed for bacterial challenge. These findings suggest that P2 molecules and surface antigens other than P2 are involved in the development of pulmonary defense against NTHi in mice. Our data may explain, in part, why patients with COPD experience recurrent NTHi infections.
authors.affiliation: Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Koyama
authors.forename: Kamruddin
authors.initials: K
authors.lastname: Ahmed
authors.forename: Jizi
authors.initials: J
authors.lastname: Zhao
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.forename: Shozaburo
authors.initials: S
authors.lastname: Onizuka
authors.forename: Keita
authors.initials: K
authors.lastname: Oma
authors.forename: Kiwao
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D018073:Haemophilus Vaccines / Q000235:genetics / Q000276:immunology; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018272:Porins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014611:Vaccination
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D018073:Haemophilus Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C069990:P6 outer membrane protein, Haemophilus; D018272:Porins; C451502:ompP2 protein, Haemophilus influenzae