title: A novel microbe-based treatment that attenuates the inflammatory profile in a mouse model of allergic airway disease.
abstract: There is an unmet need for effective new and innovative treatments for asthma. It is becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in a model of allergic airway disease in mice. BALB/c mice were exposed intranasally to house dust mite (HDM) for two weeks. Mice were treated prophylactically via subcutaneous route with either KB or placebo for one week prior to HDM exposure and throughout the two week exposure period. 24 hours after the last exposure, lungs were analysed for inflammatory cell infiltrate, gene expression, cytokine levels, goblet cell metaplasia, and serum was analysed for allergen-specific serum IgE levels. HDM exposed mice developed goblet cell hyperplasia, elevated allergen-specific serum IgE, airway eosinophilia, and a concomitant increase in TH2 cytokines including IL-4, IL-13 and IL-5. Treatment with KB attenuated HDM-mediated airway eosinophilia, total bronchoalveolar lavage (BAL) cell numbers, BAL TH2 cytokine production, and goblet cell metaplasia. Our prophylactic intervention study illustrates the potential of subcutaneous treatment with bacterial derived biologics as a promising approach for allergic airway disease treatment.
authors.affiliation: Qu Biologics Inc., Vancouver, BC, V5T 4T5, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Bazett
authors.affiliation: University of British Columbia, Department of Medicine, Division of Respiratory Medicine, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Biala
authors.affiliation: University of British Columbia, Department of Medicine, Division of Respiratory Medicine, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Huff
authors.affiliation: Qu Biologics Inc., Vancouver, BC, V5T 4T5, Canada.
authors.forename: Momir
authors.initials: M
authors.lastname: Bosiljcic
authors.affiliation: Qu Biologics Inc., Vancouver, BC, V5T 4T5, Canada.
authors.forename: Hal
authors.initials: H
authors.lastname: Gunn
authors.affiliation: Qu Biologics Inc., Vancouver, BC, V5T 4T5, Canada.|University of British Columbia, Department of Medicine, Division of Endocrinology, CeMCOR, Vancouver, BC, V5Z 1M9.
authors.forename: Shirin
authors.initials: S
authors.lastname: Kalyan
authors.affiliation: University of British Columbia, Department of Medicine, Division of Respiratory Medicine, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hirota
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054413:Chemokine CCL11 / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D018793:Interleukin-13 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007709:Klebsiella / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E