Vaccination against Pseudomonas aeruginosa pneumonia in immunocompromised mice
Jennifer M Scarff1, Joanna B Goldberg
1Department of Microbiology, University of Virginia Health System, Charlottesville, Virginia, USA.
Abstract:
Immunocompromised patients are highly susceptible to infection with Pseudomonas aeruginosa. Our laboratory previously showed 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 nontreated counterparts, demonstrating 50% lethal doses 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 of the mice prior to treatment 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.
Insights
This study shows that an attenuated Salmonella vaccine protects immunocompromised mice against Pseudomonas aeruginosa pneumonia. While vaccination improves survival, antibodies also play a critical role in combating this infection.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Immunocompromised individuals face severe risks from Pseudomonas aeruginosa infections.
- Previous research demonstrated an attenuated Salmonella vaccine's efficacy against P. aeruginosa in wild-type mice.
Purpose of the Study:
- To evaluate the effectiveness of an attenuated Salmonella vaccine expressing P. aeruginosa O antigen in immunocompromised mouse models.
- To investigate the role of white blood cells and antibodies in protection against P. aeruginosa pneumonia in immunocompromised states.
Main Methods:
- Induction of leukopenia and neutropenia using cyclophosphamide (Cy) or RB6-8C5 antibody in mice.
- Intranasal challenge with P. aeruginosa post-vaccination or vector immunization.
- Assessment of survival rates, bacterial loads in lungs, liver, and spleen, and lung permeability.
- Measurement of antibody titers before and after challenge.
Main Results:
- Immunocompromised mice exhibited significantly lower lethal doses and increased bacterial dissemination compared to wild-type mice.
- Vaccination prior to immune suppression improved survival and reduced bacterial loads.
- Antibody administration at the time of infection also enhanced survival and lowered bacterial counts.
- Immune suppression treatments did not affect antibody titers but reduced vaccine efficacy compared to untreated vaccinated mice.
Conclusions:
- White blood cells are crucial for host defense against P. aeruginosa pneumonia.
- The attenuated Salmonella vaccine offers partial protection in immunocompromised hosts, highlighting the importance of antibodies.
- Combined strategies involving vaccination and antibody therapy may be necessary for effective P. aeruginosa infection control in vulnerable populations.
