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Infection and Immunity, February 2006, p. 975-983, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.975-983.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Live-Attenuated Pseudomonas aeruginosa Vaccine Elicits Outer Membrane Protein-Specific Active and Passive Protection against Corneal Infection

Tanweer S. Zaidi,1,{dagger} Gregory P. Priebe,1,2*,{dagger} and Gerald B. Pier1

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital,1 Departments of Anesthesia (Division of Critical Care) and Medicine (Division of Infectious Diseases), Children's Hospital, Boston, Massachusetts2

Received 28 June 2005/ Returned for modification 15 August 2005/ Accepted 8 November 2005

Pseudomonas aeruginosa can cause sight-threatening corneal infections in humans, particularly those who wear contact lenses. We have previously shown that a live-attenuated P. aeruginosa vaccine given intranasally protected mice against acute lethal pneumonia in a lipopolysaccharide (LPS) serogroup-specific manner. In the current study, we evaluated the protective and therapeutic efficacies, as well as the target antigens, of this vaccine in a murine corneal infection model. C3H/HeN mice were nasally immunized with the vaccine (an aroA deletion mutant of strain PAO1, designated PAO1{Delta}aroA) or with Escherichia coli as a control and were challenged 3 weeks later by inoculating the scratch-injured cornea with P. aeruginosa. For passive prophylaxis and therapy, we utilized a serum raised in rabbits nasally immunized with PAO1{Delta}aroA or E. coli. Outcome measures included corneal pathology scores and, in some experiments, reductions in total and internalized bacterial CFU. We found that both active and passive immunization reduced corneal pathology scores after challenge with a variety of P. aeruginosa strains, including several serogroup-heterologous strains. Even when given therapeutically starting as late as 24 h after infection, the rabbit antiserum to PAO1{Delta}aroA was effective at reducing corneal pathology scores. Immunotherapy of established infections also reduced the numbers of total and internalized corneal P. aeruginosa bacteria. Experiments using absorbed sera showed that the protective antibodies are specific to outer membrane proteins. Thus, live-attenuated P. aeruginosa vaccines delivered nasally protect against corneal infections in mice and potentially can be used to prepare passive therapy reagents for the treatment of established P. aeruginosa corneal infections caused by diverse LPS serogroups.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: (617) 525-2663. Fax: (617) 525-2510. E-mail: gpriebe{at}rics.bwh.harvard.edu.

Editor: J. T. Barbieri

{dagger} T.S.Z. and G.P.P. contributed equally to this work.

Infection and Immunity, February 2006, p. 975-983, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.975-983.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zaidi, T., Pier, G. B. (2008). Prophylactic and Therapeutic Efficacy of a Fully Human Immunoglobulin G1 Monoclonal Antibody to Pseudomonas aeruginosa Alginate in Murine Keratitis Infection. Infect. Immun. 76: 4720-4725 [Abstract] [Full Text]  
  • Green, S. N., Sanders, M., Moore, Q. C. III, Norcross, E. W., Monds, K. S., Caballero, A. R., McDaniel, L. S., Robinson, S. A., Onwubiko, C., O'Callaghan, R. J., Marquart, M. E. (2008). Protection from Streptococcus pneumoniae Keratitis by Passive Immunization with Pneumolysin Antiserum. IOVS 49: 290-294 [Abstract] [Full Text]  


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