Efficacy of a Pseudomonas Aeruginosa Vaccine in Immunocompromised Mice

Pseudomonas aeruginosa is an important opportunistic pathogen, infecting primarily immunocompromised individuals and cystic fibrosis (CF) patients. We previously showed that intranasal vaccination with an attenuated Salmonella enterica serovar Typhimurium strain that expresses the O antigen from an O11 serotype of P. aeruginosa protected mice from an intranasal challenge with P. aeruginosa. Administration of immune sera to naïve mice at the time of infection was also able to confer protection against a lung infection (1). Here, we sought to further characterize the immune response to this vaccine and also to investigate its efficacy in clinically relevant mouse models of immunocompromise and CF. We demonstrated that both leukopenic and neutropenic mice are hypersusceptible to infection with P. aeruginosa and this is characterized by dissemination to the spleen and liver. Vaccination and administration of sera to mice at the time of infection were able to reduce the susceptibility of the immunocompromised mice and this was associated with a decreased dissemination of bacteria compared to control mice. We also investigated the adaptive immune response following vaccination. Serum antibodies were shown to persist in wild type mice for eighteen months after a single vaccination. The antibody response following vaccination was shown to be B cell and T cell, particularly CD4 cell, dependent. T cells from vaccinated mice were, however, unable to transfer protection against a P. aeruginosa challenge to naïve mice. Administration of vaccine sera to CF mice was also investigated for its efficacy in preventing P. aeruginosa infection. CF mice receiving vaccine sera had increased survival compared to control mice. However, analysis of bacterial load yielded no difference between mice receiving vaccine sera and control mice. Passive vaccination of CF mice naturally infected with P. aeruginosa was able to clear the ii bacteria from only mice that had low anti-Pseudomonas antibody titers prior to administration of sera. Interestingly, this effect was seen with both the administration of vaccine and vector sera. This work showed the longevity of the antibody response following vaccination and further elucidates the immune response to vaccination. We also demonstrated protection from vaccination in clinically relevant models of infection.

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