title: Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.
abstract: The goal of this study was to investigate if antibodies raised against N'-terminal Pseudomonas aeruginosa (Pa) flagellin could afford protection in two lethal mouse models of Pa infection. To that end, rabbit polyclonal antibodies were generated against the N'-terminal domains (amino acids 1-156) of recombinant Pa01 or Salmonella muenchen flagellins, termed anti-N'-fla-b and anti-N'-fla-Sm, respectively. In vitro, anti-N'-fla-b but not anti-N'-fla-Sm IgG specifically recognized recombinant and Pa endogenous flagellin type b proteins, total bacterial lysates of Pa type b, and inhibited Pa01 invasion into A549 cells. In vivo, administration of anti-N'-fla-b afforded a remarkable improvement in survival in lethal peritonitis (90% vs. 12% in control; p<0.001) and burn infection (83% vs. 8-17% in control groups; p<0.005) Pa models. These findings would suggest that the N'-terminal domain of Pa flagellin harbors critically important bioactive domains and that an antibody-targeted, neutralization approach directed at this region could provide a novel therapeutic strategy to combat Pa infection.
authors.affiliation: XTL Biopharmaceuticals, Rehovot, Israel.
authors.forename: Lewis F
authors.initials: LF
authors.lastname: Neville
authors.forename: Yoav
authors.initials: Y
authors.lastname: Barnea
authors.forename: Orly
authors.initials: O
authors.lastname: Hammer-Munz
authors.forename: Eyal
authors.initials: E
authors.lastname: Gur
authors.forename: Boris
authors.initials: B
authors.lastname: Kuzmenko
authors.forename: Hamutal
authors.initials: H
authors.lastname: Kahel-Raifer
authors.forename: Rachel
authors.initials: R
authors.lastname: Eren
authors.forename: Adi
authors.initials: A
authors.lastname: Elkeles
authors.forename: Kanneganti G K
authors.initials: KG
authors.lastname: Murthy
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Salzman
authors.forename: Shlomo
authors.initials: S
authors.lastname: Dagan
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.forename: Shiri
authors.initials: S
authors.lastname: Navon-Venezia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D016415:Sequence Alignment; D015996:Survival Rate
chemical_list: D000907:Antibodies, Bacterial; D005408:Flagellin