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Infection and Immunity, November 2005, p. 7705-7717, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7705-7717.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intranasal Immunization Strategy To Impede Pilin-Mediated Binding of Pseudomonas aeruginosa to Airway Epithelial Cells

Jennifer C. Hsieh,^1, Doris M. Tham,^1, Weijun Feng,¹ Fan Huang,¹ Selamawit Embaie,¹ Keyi Liu,¹ Deborah Dean,² Ralf Hertle,^3,4 David J. FitzGerald,³ and Randall J. Mrsny^1*

Trinity BioSystems, Inc., 1455 Adams Dr., Suite 1317, Menlo Park, California 94025-1438,¹ Department of Medicine, University of California at San Francisco School of Medicine, San Francisco, California 94143, and Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, California 94609,² Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, Bethesda, Maryland 20892-4255,³ University of Tuebingen, Institute of Microbiology/Membrane Physiology, Auf der Morgenstelle 28, D-72076 Tuebingen, Germany⁴

Received 23 May 2005/ Returned for modification 13 July 2005/ Accepted 10 August 2005

Prevention of pulmonary Pseudomonas aeruginosa infections represents a critical unmet medical need for cystic fibrosis (CF) patients. We have examined the tenet that a mucosal immunization approach can reduce interactions of a piliated form of this opportunistic pathogen with respiratory epithelial cells. Vaccinations were performed using ntPEpilinPAK, a protein chimera composed of a nontoxic form of P. aeruginosa exotoxin A (ntPE), where the C-terminal loop amino acid sequence of the PAK strain pilin protein was inserted in place of the ntPE Ib domain. Intranasal (i.n.) immunization of BALB/c mice with ntPEpilinPAK generated both serum and saliva immune responses. A series of in vitro studies showed that diluted samples of saliva obtained from immunized mice reduced pilin-dependent P. aeruginosa binding to polarized human tracheal epithelial cells, protected human pulmonary epithelial cells from cytotoxic actions associated with bacterial challenge, and reduced exotoxin A toxicity. Overall, i.n. administration of ntPEpilinPAK induced mucosal and systemic immune responses that may be beneficial for blocking early stage adhesion and/or infection events of epithelial cell-P. aeruginosa interactions at oropharyngeal surfaces.

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* Corresponding author. Mailing address: Trinity BioSystems, Inc., 1455 Adams Dr., Suite 1317, Menlo Park, CA 94025-1438. Phone: (650) 566-0781. Fax: (650) 566-0793. E-mail: rmrsny{at}trinitybiosystems.com.

Editor: J. T. Barbieri

Both authors contributed equally to this work.

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Infection and Immunity, November 2005, p. 7705-7717, Vol. 73, No. 11
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.11.7705-7717.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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