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Infection and Immunity, January 2004, p. 66-75, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.66-75.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Development of an Intranasal Vaccine To Prevent Urinary Tract Infection by Proteus mirabilis

Xin Li,1 C. Virginia Lockatell,2 David E. Johnson,2 M. Chelsea Lane,1 John W. Warren,3 and Harry L. T. Mobley1*

Department of Microbiology and Immunology,1 Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine,3 Division of Research Service, Veterans Administration Medical Center, Baltimore, Maryland 212012

Received 11 June 2003/ Returned for modification 3 September 2003/ Accepted 17 September 2003

Proteus mirabilis commonly infects the complicated urinary tract and is associated with urolithiasis. Stone formation is caused by bacterial urease, which hydrolyzes urea to ammonia, causing local pH to rise, and leads to the subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) crystals. To prevent these infections, we vaccinated CBA mice with formalin-killed bacteria or purified mannose-resistant, Proteus-like (MR/P) fimbriae, a surface antigen expressed by P. mirabilis during experimental urinary tract infection, via four routes of immunization: subcutaneous, intranasal, transurethral, and oral. We assessed the efficacy of vaccination using the CBA mouse model of ascending urinary tract infection. Subcutaneous or intranasal immunization with formalin-killed bacteria and intranasal or transurethral immunization with purified MR/P fimbriae significantly protected CBA mice from ascending urinary tract infection by P. mirabilis (P < 0.05). To investigate the potential of MrpH, the MR/P fimbrial tip adhesin, as a vaccine, the mature MrpH peptide (residues 23 to 275, excluding the signal peptide), and the N-terminal receptor-binding domain of MrpH (residues 23 to 157) were overexpressed as C-terminal fusions to maltose-binding protein (MBP) and purified on amylose resins. Intranasal immunization of CBA mice with MBP-MrpH (residues 23 to 157) conferred effective protection against urinary tract infection by P. mirabilis (P < 0.002).

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201. Phone: (410) 706-0466. Fax: (410) 706-6751. E-mail: hmobley{at}umaryland.edu.

Editor: J. N. Weiser

Infection and Immunity, January 2004, p. 66-75, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.66-75.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alamuri, P., Eaton, K. A., Himpsl, S. D., Smith, S. N., Mobley, H. L. T. (2009). Vaccination with Proteus Toxic Agglutinin, a Hemolysin-Independent Cytotoxin In Vivo, Protects against Proteus mirabilis Urinary Tract Infection. Infect. Immun. 77: 632-641 [Abstract] [Full Text]  
  • Nielubowicz, G. R., Smith, S. N., Mobley, H. L. T. (2008). Outer Membrane Antigens of the Uropathogen Proteus mirabilis Recognized by the Humoral Response during Experimental Murine Urinary Tract Infection. Infect. Immun. 76: 4222-4231 [Abstract] [Full Text]  
  • Jacobsen, S. M., Stickler, D. J., Mobley, H. L. T., Shirtliff, M. E. (2008). Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis. Clin. Microbiol. Rev. 21: 26-59 [Abstract] [Full Text]  
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  • Li, X., Erbe, J. L., Lockatell, C. V., Johnson, D. E., Jobling, M. G., Holmes, R. K., Mobley, H. L. T. (2004). Use of Translational Fusion of the MrpH Fimbrial Adhesin-Binding Domain with the Cholera Toxin A2 Domain, Coexpressed with the Cholera Toxin B Subunit, as an Intranasal Vaccine To Prevent Experimental Urinary Tract Infection by Proteus mirabilis. Infect. Immun. 72: 7306-7310 [Abstract] [Full Text]  


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