Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa

Teiji Sawa, Emi Ito, Vinh Huu Nguyen, Matthew Haight

Research output: Contribution to journalReview article

28 Scopus citations

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 antigenbinding 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.

Original languageEnglish (US)
Pages (from-to)2843-2852
Number of pages10
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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Keywords

  • Antibody
  • PcrV
  • Pseudomonas aeruginosa
  • Type III secretion system
  • V-antigen

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