Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity

• Published in: Infection and Immunity Vol. 77; no. 3; pp. 1083 - 1090
• Main Authors: Baer, Mark, Sawa, Teiji, Flynn, Peter, Luehrsen, Kenneth, Martinez, David, Wiener-Kronish, Jeanine P, Yarranton, Geoffrey, Bebbington, Christopher
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2009; American Society for Microbiology (ASM)
• Subjects: ADP Ribose Transferases - immunology; Animals; Antibacterial activity; Antibodies; Antibody Specificity; Antigens, Bacterial - immunology; Bacterial Toxins - immunology; Cytotoxicity, Immunologic - immunology; Enzyme-Linked Immunosorbent Assay; Exotoxins; Exotoxins - immunology; Fab; Humans; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - therapeutic use; Infection; Injuries; Lung; Male; Mice; Mice, Inbred BALB C; Microbial Immunity and Vaccines; Mortality; Opportunist infection; Pathogens; Pore Forming Cytotoxic Proteins - immunology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa Exotoxin A; Pseudomonas Infections - immunology; Pseudomonas Infections - prevention & control; Recombinant Proteins - biosynthesis; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; Structural proteins; Virulence Factors - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00815-08

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.