PLGA-encapsulation of the Pseudomonas aeruginosa PopB vaccine antigen improves Th17 responses and confers protection against experimental acute pneumonia.

Abstract

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.

• Authors: Matthew M Schaefers, Biyan Duan, Boaz Mizrahi, Roger Lu, Gally Reznor, Daniel S Kohane, Gregory P Priebe
• Journal: Vaccine (Vaccine) Vol. 36 Issue 46 Pg. 6926-6932 (11 12 2018) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 30314911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• Drug Carriers
• Il17a protein, mouse
• Interleukin-17
• PopB protein, Pseudomonas aeruginosa
• Pseudomonas Vaccines
• Vaccines, Subunit
• Vaccines, Synthetic
• Polylactic Acid-Polyglycolic Acid Copolymer

Topics

• Administration, Intranasal
• Animals
• Antigens, Bacterial (administration & dosage, immunology)
• Bacterial Load
• Bacterial Proteins (administration & dosage, immunology)
• Disease Models, Animal
• Drug Carriers (administration & dosage)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Interleukin-17 (analysis)
• Lung (microbiology, pathology)
• Pneumonia, Bacterial (prevention & control)
• Polylactic Acid-Polyglycolic Acid Copolymer (administration & dosage)
• Pseudomonas Infections (prevention & control)
• Pseudomonas Vaccines (administration & dosage, immunology)
• Survival Analysis
• Th17 Cells (immunology)
• Vaccines, Subunit (administration & dosage, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)