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	Mark Baer, Teiji Sawa, Peter Flynn, Kenneth Luehrsen, David Martinez, Jeanine P Wiener-Kronish, Geoffrey Yarranton, Christopher Bebbington
Journal	Infection and immunity (Infect Immun) Vol. 77 Issue 3 Pg. 1083-90 (Mar 2009) ISSN: 1098-5522 [Electronic] United States
PMID	19103766 (Publication Type: Journal Article)
Chemical References	Antigens, Bacterial Bacterial Toxins Exotoxins Immunoglobulin Fab Fragments Pore Forming Cytotoxic Proteins Recombinant Proteins Virulence Factors antigen V, Pseudomonas ADP Ribose Transferases
Topics	ADP Ribose Transferases (immunology) Animals Antibody Specificity Antigens, Bacterial (immunology) Bacterial Toxins (immunology) Cytotoxicity, Immunologic (immunology) Enzyme-Linked Immunosorbent Assay Exotoxins (immunology) Humans Immunoglobulin Fab Fragments (immunology, therapeutic use) Male Mice Mice, Inbred BALB C Pore Forming Cytotoxic Proteins (immunology) Pseudomonas Infections (immunology, prevention & control) Pseudomonas aeruginosa (immunology) Recombinant Proteins (biosynthesis, immunology, therapeutic use) Virulence Factors (immunology) Pseudomonas aeruginosa Exotoxin A

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