title: Flagellin and pilin immunization against multi-drug resistant Pseudomonas aeruginosa protects mice in the burn wound sepsis model.
abstract: Pseudomonas aeruginosa is a formidable pathogen and a major threat to burn patients. Antimicrobial therapy is often unsuccessful because P. aeruginosa can develop multi-drug resistance; thus, immunotherapy and vaccine can be a rational alternative. Flagella and type IV pili have been identified as important virulence factors in the colonization and pathogenesis of P. aeruginosa in burn wound infections. Immunogenicity and efficacy of mixed recombinant full-length type b flagellin (r-b-flagellin) and recombinant PilA (r-PilA) as candidate vaccines were assessed by measuring humoral and cellular responses, using an experimental burned mouse model. Primary immunization with "r-b-flagellin+r-PilA" followed by two booster shots was sufficient to generate a robust humoral response, which was predominantly a Th2 response consisting mainly of subtype IgG1 and low levels of IgG2a. Analysis of the cytokine response among immunized mice showed an increased production of IL-4, INF-γ and IL-17 by splenocytes upon stimulation by "r-b-flagellin+r-PilA". Opsonophagocytosis assays confirmed the enhanced killing of bacteria by anti "r-b-flagellin+r-PilA" immune sera. These antibodies were also able to reduce bacterial load in the site of original infection into the liver and spleen of challenged mice. The reduction of systemic bacterial spread resulted in an increased survival rate of challenged immunized mice. In conclusion, immunization with "r-b-flagellin+r-PilA" proteins provides a better protective response against P. aeruginosa infection in the burn mouse model.
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Korpi
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad B
authors.initials: FB
authors.lastname: Hashemi
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: dr.irajian@gmail.com.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Irajian
authors.affiliation: Burn Research Center, Motahari Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Fatemi
authors.affiliation: Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Laghaei
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Burn Research Center, Motahari Hospital, Iran University of Medical Sciences, Tehran, Iran. Electronic address: bahador.behroz3@gmail.com.
authors.forename: Bahador
authors.initials: B
authors.lastname: Behrouz
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000276:immunology*; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology*; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology*; D037521:Virulence Factors
chemical_list: D037521:Virulence Factors; D005408:Flagellin; D036781:Fimbriae Proteins
keywords: Antibody; Burn; Immunization; Pseudomonas aeruginosa; r-PilA; r-b-flagellin