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

Abstract

Pseudomonas aeruginosa 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 P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant microorganism. We propose that identifying the vaccine-induced correlates of protection against P. aeruginosa will facilitate the development of a vaccine against this pathogen. In this study, we studied the mechanistic correlates of protection of a curdlan-adjuvanted P. aeruginosa whole-cell vaccine (WCV) delivered intranasally. WCV significantly decreased bacterial loads in the respiratory tract after intranasal P. aeruginosa 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 boost. 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 mice alone protected naive mice against P. aeruginosa, supporting the role of antibodies in clearing P. aeruginosa. We observed that in the absence of T-cell dependent antibody production, mice vaccinated with WCV were still able to reduce bacterial loads. Our results collectively highlight the importance of the humoral immune response for protection against P. aeruginosa and suggest that the production of T cell-independent antibodies may be sufficient for bacterial clearance induced by whole-cell P. aeruginosa vaccination.

Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency

“…S8). Together, the trends from these data showed the importance of neutrophil recruitment in the response against P. aeruginosa infection (30,47,48).…”

“…Treatment options for multidrug-resistant P. aeruginosa are limited (28,29). Many experimental vaccines have demonstrated potential, but none have been clinically approved (30)(31)(32)(33)(34).…”

Outer Membrane Vesicles Displaying a Heterologous PcrV-HitA Fusion Antigen Promote Protection against Pulmonary Pseudomonas aeruginosa Infection

“…However, excessive production of TNF-α or other proinflammatory cytokines in the lungs of PBS-, rOMV-N-, or PH-immunized animals will result in immune dysregulation, leading to ineffectively clearing bacteria, loss of lung function, and eventually death. Intriguingly, Sen-Kilic et al recently highlighted the importance of the humoral immune response for protection against P. aeruginosa infection and showed that passive immunization with serum from mice vaccinated with a curdlan-adjuvanted P. aeruginosa whole-cell vaccine (WCV) alone protected naive mice against P. aeruginosa ( 64 ). However, our results in antibody passive immunization and T-cell depletion were inconsistent with their observations.…”

Long-Term Analysis of Pertussis Vaccine Immunity to Identify Potential Markers of Vaccine-Induced Memory Associated With Whole Cell But Not Acellular Pertussis Immunization in Mice

“…Enzyme linked immunosorbent assay (ELISA) was utilized to measure antigen-specific antibodies in the serum of immunized mice (52)(53)(54). After euthanasia, blood was collected in BD Microtainer serum separator tubes (BD, Cat.…”