Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia

Abstract

<i>Pseudomonas aeruginosa</i> is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against <i>P. aeruginosa</i> could help prevent infections caused by this highly antibiotic-resistant microorganism. We propose that identifying the vaccine-induced correlates of protection against <i>P. aeruginosa</i> will facilitate the development of a vaccine against this pathogen. In this study, we investigated the mechanistic correlates of protection of a curdlan-adjuvanted <i>P. aeruginosa</i> whole-cell vaccine (WCV) delivered intranasally. The WCV significantly decreased bacterial loads in the respiratory tract after intranasal <i>P. aeruginosa</i> challenge and raised antigen-specific antibody titers. To study the role of B and T cells during vaccination, anti-CD4, -CD8, and -CD20 depletions were performed prior to WCV vaccination and boosting. The depletion of CD4⁺, CD8⁺, or CD20⁺ cells had no impact on the bacterial burden in mock-vaccinated animals. However, depletion of CD20⁺ B cells, but not CD8⁺ or CD4⁺ T cells, led to the loss of vaccine-mediated bacterial clearance. Also, passive immunization with serum from WCV group mice alone protected naive mice against <i>P. aeruginosa</i>, supporting the role of antibodies in clearing <i>P. aeruginosa</i> We observed that in the absence of T cell-dependent antibody production, mice vaccinated with the WCV were still able to reduce bacterial loads. Our results collectively highlight the importance of the humoral immune response for protection against <i>P. aeruginosa</i> and suggest that the production of T cell-independent antibodies may be sufficient for bacterial clearance induced by whole-cell <i>P. aeruginosa</i> vaccination.