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Infection and Immunity, March 2009, p. 1083-1090, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.00815-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity{triangledown}

Mark Baer,1 Teiji Sawa,2,{dagger} Peter Flynn,1,{ddagger} Kenneth Luehrsen,1 David Martinez,1 Jeanine P. Wiener-Kronish,2,§ Geoffrey Yarranton,1 and Christopher Bebbington1*

Kalobios Pharmaceuticals, Inc., 260 East Grand Avenue, South San Francisco, California 94080,1 Department of Anesthesia and Perioperative Care, University of California, San Francisco, 35 Lucerne Street #3, San Francisco, California 941032

Received 1 July 2008/ Returned for modification 31 July 2008/ Accepted 15 December 2008

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.

* Corresponding author. Mailing address: Kalobios Pharmaceuticals, Inc., 260 East Grand Avenue, South San Francisco, CA 94080. Phone: (650) 843-1897, ext. 305. Fax: (650) 843-1896. E-mail: cbebbington{at}kalobios.com

{triangledown} Published ahead of print on 22 December 2008.

Editor: J. B. Bliska

{dagger} Present address: Department of Anesthesia, Kyoto First Red Cross Hospital, Honmachi 15-749, Higashiyama, Kyoto 605-0981, Japan.

{ddagger} Present address: Ren Pharmaceuticals, 270 East Grand Avenue, South San Francisco, CA 94080.

§ Present address: Department of Anesthesia and Critical Care, Massachusetts General Hospital, GRB 444, 55 Fruit Street, Boston, MA.

Infection and Immunity, March 2009, p. 1083-1090, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.00815-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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