title: Immunogenicity of Pseudomonas aeruginosa recombinant b-type fagellin as a vaccine candidate: Protective efficacy in a murine burn wound sepsis model.
abstract: Pseudomonas aeruginosa (PA) is a formidable opportunistic pathogen among patients with burn wound infections. Antimicrobial therapy is often unsuccessful because PA can develop multi-drug resistance; thus, immunotherapy can be a rational alternative. The goal of this study was to evaluate the immunogenicity recombinant type b flagellin (r-b-flagellin) as a potential vaccine against P. aeruginosa in a mouse model for burn wound sepsis. Primary immunization with r-b-flagellin (10μg) followed by two booster shots was sufficient to generate a robust humoral response, which was predominantly a T helper 2 (Th2) type response consisting mainly of subtype IgG1 and low levels of IgG2a. Analysis of the Th1-Th2 response among immunized mice showed an increased production of IL-4, INF-γ and IL-17 by splenocytes upon stimulation by r-b-flagellin. Opsono-phagocytosis assays confirmed the enhanced killing of bacteria by anti r-b-flagellin immune sera. These antibodies were also able to inhibit motility of P. aeruginosa and afforded protection to immunized mice by reducing bacterial load in the site of original infection into the liver of challenged mice. The reduction of systemic bacterial spread resulted in an increase in the survival rate of challenged immunized mice. In conclusion, immunization of mice with r-b-flagellin protein increased the level of humoral and cellular immune response and led to an efficacious protection against P. aeruginosa infection in the burn mouse model.
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 Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
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 Plastic and Reconstructive Surgery, Burn Research Center, Hazrat Fatima 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: Gholamreza
authors.initials: G
authors.lastname: Irajian
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahbubeh
authors.initials: M
authors.lastname: Bahroudi
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: hashemi@fbh.hiv.
authors.forename: Farhad B
authors.initials: FB
authors.lastname: Hashemi
keywords: Antibody; Burn; Immunization; Pseudomonas aeruginosa; Recombinant flagellin