The Pseudomonas aeruginosa type III secretion system protein PopB and its chaperon protein PcrH, when co-administered with the adjuvant curdlan, elicit Th17 responses after intranasal immunization of mice. These PopB/PcrH-curdlan vaccines protect mice against acute lethal pneumonia in an IL-17-dependent fashion involving CD4 helper T cells secreting IL-17 (Th17 cells). In this study, we tested whether encapsulation of PopB/PcrH in poly-lactic-co-glycolic acid (PLGA) nanoparticles could elicit Th17 responses to PopB. Recombinant PopB/PcrH or PcrH alone was encapsulated into PLGA nanoparticles. Mice (FVB/N) were intranasally immunized with the PLGA-PopB/PcrH nanoparticles, PLGA-PcrH nanoparticles, PLGA alone, or PopB/PcrH alone. The protective efficacy was assessed in an acute lung infection model with a lethal dose of an ExoU-producing version of P. aeruginosa strain PAO1. Th17 responses were assayed by intracellular flow cytometry and by ELISA for IL-17 in supernatants of splenocytes co-cultured with purified PopB/PcrH. PLGA-PopB/PcrH-immunized mice showed 3-4-fold higher Th17 responses both in the lung and in the spleen compared to mice immunized with empty PLGA or PopB/PcrH alone. After challenge with P. aeruginosa, PLGA-PopB/PcrH-immunized mice showed significantly lower bacterial counts in the lungs and improved survival. In conclusion, encapsulation of PopB/PcrH in PLGA nanoparticles can elicit Th17 responses to intranasal vaccination and protect mice against acute lethal P. aeruginosa pneumonia.
Keywords: IL-17; Nanoparticle; PLGA; Pseudomonas aeruginosa; Th17; Vaccine.
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