title: An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute lung injury and mortality through the delivery of exotoxins by the type III secretion system (TTSS). PcrV is an important structural protein of the TTSS. An engineered human antibody Fab fragment that binds to the P. aeruginosa PcrV protein with high affinity has been identified and has potent in vitro neutralization activity against the TTSS. The instillation of a single dose of Fab into the lungs of mice provided protection against lethal pulmonary challenge of P. aeruginosa and led to a substantial reduction of viable bacterial counts in the lungs. These results demonstrate that blocking of the TTSS by a Fab lacking antibody Fc-mediated effector functions can be sufficient for the effective clearance of pulmonary P. aeruginosa infection.
authors.affiliation: Kalobios Pharmaceuticals, Inc, South San Francisco, California 94080, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Baer
authors.forename: Teiji
authors.initials: T
authors.lastname: Sawa
authors.forename: Peter
authors.initials: P
authors.lastname: Flynn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Luehrsen
authors.forename: David
authors.initials: D
authors.lastname: Martinez
authors.forename: Jeanine P
authors.initials: JP
authors.lastname: Wiener-Kronish
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Yarranton
authors.forename: Christopher
authors.initials: C
authors.lastname: Bebbington
mesh_terms: D036002:ADP Ribose Transferases / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use; D037521:Virulence Factors / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D007140:Immunoglobulin Fab Fragments; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C118546:antigen V, Pseudomonas