title: Bivalent flagellin immunotherapy protects mice against Pseudomonas aeruginosa infections in both acute pneumonia and burn wound models.
abstract: Pseudomonas aeruginosa infections are a serious challenge to therapy because of the complex pathogenesis and paucity of new effective antibiotics, thus renewing interest in antibody-based therapeutic strategies. Immunotherapy strategies typically target selected virulence factors that are expressed by the majority of clinical strains of P. aeruginosa, particularly because virulence factors mediate infection. Type a and b flagellins (flagellin a+b) of P. aeruginosa are acute virulence factors that play a major role in the establishment of infection. Here we evaluate the protective efficacy of antibodies raised against "flagellin a+b" in both acute pneumonia and burn models. A combination strategy using antibodies against "flagellin a+b" provided greater protection against cell invasion and enhanced opsono-phagocytosis and decreased motility of P. aeruginosa strains, compared to strategies using antibodies against a single flagellin. Antibodies against "flagellin a+b"-protected mice infected with P. aeruginosa strains significantly reduced bacterial dissemination from the site of infection to the liver and spleen. Passive immunization with antibodies against "flagellin a+b" led to an efficacious protection against P. aeruginosa infection in both acute pneumonia and burn models.
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hosein
authors.initials: H
authors.lastname: Ahmadi
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Bahador
authors.initials: B
authors.lastname: Behrouz
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: ghirajian.vac@gmail.com.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Irajian
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nour
authors.initials: N
authors.lastname: Amirmozafari
authors.affiliation: Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Naghavi
mesh_terms: D000072283:A549 Cells; D000208:Acute Disease; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000627:therapeutic use; D015153:Blotting, Western; D002056:Burns / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005408:Flagellin / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000502:physiology; D011817:Rabbits
chemical_list: D000907:Antibodies, Bacterial; D005408:Flagellin
keywords: Acute pneumonia; Antibody; Burn; Pseudomonas aeruginosa; “Flagellin a+b”