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Infection and Immunity, November 2001, p. 6962-6969, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6962-6969.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Dual-Function Vaccine for Pseudomonas aeruginosa: Characterization of Chimeric Exotoxin A-Pilin Protein

Ralf Hertle,1,dagger Randall Mrsny,2 and David J. Fitzgerald1,*

Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, Bethesda, Maryland 20892-4255,1 and Genentech, Inc., South San Francisco, California 94080-49902

Received 26 June 2001/Returned for modification 26 July 2001/Accepted 7 August 2001

Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis patients. Strategies to prevent colonization by this bacterium and/or neutralize its virulence factors are clearly needed. Here we characterize a dual-function vaccine designed to generate antibodies to reduce bacterial adherence and to neutralize the cytotoxic activity of exotoxin A. To construct the vaccine, key sequences from type IV pilin were inserted into a vector encoding a nontoxic (active-site deletion) version of exotoxin A. The chimeric protein, termed PE64Delta 553pil, was expressed in Escherichia coli, refolded to a near-native conformation, and then characterized by various biochemical and immunological assays. PE64Delta 553pil bound specifically to asialo-GM1, and, when injected into rabbits, produced antibodies that reduced bacterial adherence and neutralized the cell-killing activity of exotoxin A. Results support further evaluation of this chimeric protein as a vaccine to prevent Pseudomonas colonization in susceptible individuals.

* Corresponding author. Mailing address: Biotherapy Section, Laboratory of Molecular Biology, CCR, National Cancer Institute, Bldg. 37, 4B03, 37 Convent Dr., MSC 4255, Bethesda, MD 20892-4255. Phone: (301) 496-9457. Fax: (301) 402-1969. E-mail: djpf{at}helix.nih.gov.

dagger Present address: Institut fuer Mikrobiologie, D-72076 Tuebingen, Germany.

Infection and Immunity, November 2001, p. 6962-6969, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6962-6969.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hsieh, J. C., Tham, D. M., Feng, W., Huang, F., Embaie, S., Liu, K., Dean, D., Hertle, R., FitzGerald, D. J., Mrsny, R. J. (2005). Intranasal Immunization Strategy To Impede Pilin-Mediated Binding of Pseudomonas aeruginosa to Airway Epithelial Cells. Infect. Immun. 73: 7705-7717 [Abstract] [Full Text]  
  • Kus, J. V., Tullis, E., Cvitkovitch, D. G., Burrows, L. L. (2004). Significant differences in type IV pilin allele distribution among Pseudomonas aeruginosa isolates from cystic fibrosis (CF) versus non-CF patients. Microbiology 150: 1315-1326 [Abstract] [Full Text]  


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