title: Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes fatal acute lung infections in critically ill individuals. Its pathogenesis is associated with bacterial virulence conferred by the type III secretion system (TTSS), through which P. aeruginosa causes necrosis of the lung epithelium and disseminates into the circulation, resulting in bacteremia, sepsis, and mortality. TTSS allows P. aeruginosa to directly translocate cytotoxins into eukaryotic cells, inducing cell death. The P. aeruginosa V-antigen PcrV, a homolog of the Yersinia V-antigen LcrV, is an indispensable contributor to TTS toxin translocation. Vaccination against PcrV ensures the survival of challenged mice and decreases lung inflammation and injury. Both the rabbit polyclonal anti-PcrV antibody and the murine monoclonal anti-PcrV antibody, mAb166, inhibit TTS toxin translocation. mAb166 IgG was cloned, and a molecular engineered humanized anti-PcrV IgG antigen-binding fragment, KB001, was developed for clinical use. KB001 is currently undergoing Phase-II clinical trials for ventilator-associated pneumonia in France and chronic pneumonia in cystic fibrosis in USA. In these studies, KB001 has demonstrated its safety, a favorable pharmacokinetic profile, and promising potential as a nonantibiotic strategy to reduce airway inflammation and damage in P. aeruginosa pneumonia.
authors.affiliation: a Department of Anesthesiology ; Kyoto Prefectural University of Medicine ; Kyoto , Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Sawa
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Vinh Huu
authors.initials: VH
authors.lastname: Nguyen
authors.forename: Matthew
authors.initials: M
authors.lastname: Haight
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D055370:Lung Injury / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D011014:Pneumonia / Q000382:microbiology / Q000517:prevention & control; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology* / Q000517:prevention & control; D054406:Pseudomonas Vaccines / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D018805:Sepsis / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; C000595441:KB001 antibody; D052899:Pore Forming Cytotoxic Proteins; D054406:Pseudomonas Vaccines; C118546:antigen V, Pseudomonas
keywords: CF, cystic fibrosis; Fab, fragment antigen binding; Fc, fragment crystallizable region; MDR, multidrug resistant; MDRP, multidrug resistant Pseudomonas aeruginosa; P. aeruginosa, Pseudomonas aeruginosa; PcrV; Pseudomonas aeruginosa; TTS, type III secretory; TTSS, type III secretion system; V-antigen; VAP, ventilator-associated pneumonia; antibody; immunoglobulin G, IgG; mAb, monoclonal antibody; type III secretion system