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Clin. Vaccine Immunol. doi:10.1128/CVI.00419-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Vaccination Against Pseudomonas aeruginosa Pneumonia in Immunocompromised Mice

Department of Microbiology, University of Virginia Health System, Charlottesville, VA

^* To whom correspondence should be addressed. Email: jbg2b{at}virginia.edu.

	Abstract

Immunocompromised patients are highly susceptible to infection with Pseudomonas aeruginosa. Our laboratory has previously shown that intranasal administration of an attenuated Salmonella strain expressing the P. aeruginosa lipopolysaccharide O antigen was effective in clearing bacteria and preventing mortality in wild-type mice after intranasal challenge. We were interested in investigating the efficacy of this vaccine strategy in immunocompromised mice. Mice rendered leukopenic or neutropenic by intraperitoneal treatment with cyclophosphamide (Cy) or RB6-8C5 antibody, respectively, were more susceptible to P. aeruginosa pneumonia than their non-treated counterparts, demonstrating LD₅₀s several logs lower than that in wild-type mice. This hypersusceptiblity was also associated with bacterial dissemination to the liver and spleen and increased lung permeability in Cy mice. Vaccination prior to treatment of the mice resulted in better survival and lower bacterial loads compared to vector-immunized mice. Although the treatments had no effect on antibody titers, this level of protection was still lower than that seen in untreated vaccinated mice. Administration of antibodies directly to the site of infection at the time of bacterial delivery prolonged survival and lowered bacterial loads in the immunocompromised mice. These results demonstrate the importance of white blood cells while still suggesting a critical role for antibodies in protection against P. aeruginosa infection.