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Updated: Aug 7, 2026
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa
Sukumar Saha1, Fumihiko Takeshita, Shin Sasaki
1Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Abstract:
For efficacious vaccine development against Pseudomonas aeruginosa (P. aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three different plasmids each targeting a fusion of outer membrane proteins (OprF/OprI), a protein regulating type III secretion system (PcrV), or an appendage (PilA) were prepared and mice were immunized with single (monovalent) or a combination of these plasmids (multivalent) via intramuscular electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine via imEPT induced the most potent protection against lethal pneumonia. Although the serum levels of IgG binding to whole bacteria cells were comparable between groups, the strongest immune protection was associated with the serum levels of Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and macrophages in the bronchoalveolar lavage following intranasal challenge. These results implied the possible clinical application of multivalent DNA vaccine against P. aeruginosa.
Insights
Multivalent DNA vaccines targeting outer membrane proteins, PcrV, and PilA show promise for Pseudomonas aeruginosa (P. aeruginosa) infection. Intramuscular electroporation (imEPT) with these vaccines induced potent protection against pneumonia in mice.
Area of Science:
- * Infectious Disease Research
- * Vaccinology
- * Bacterial Pathogenesis
Background:
- * Pseudomonas aeruginosa (P. aeruginosa) poses a significant threat, necessitating effective vaccine strategies.
- * Outer membrane proteins (OprF/OprI), type III secretion system regulator (PcrV), and appendage protein (PilA) are key P. aeruginosa targets.
- * DNA vaccines offer a flexible platform for developing vaccines against challenging pathogens.
Purpose of the Study:
- * To evaluate the immunogenicity and protective efficacy of a multivalent DNA vaccine against P. aeruginosa.
- * To compare different immunization methods, including intramuscular electroporation (imEPT) and gene gun delivery.
- * To identify key immune correlates of protection.
Main Methods:
- * Preparation of three distinct DNA plasmids encoding P. aeruginosa antigens: OprF/OprI fusion, PcrV, and PilA.
- * Immunization of mice with monovalent or multivalent DNA vaccines using imEPT or gene gun.
- * Assessment of immune responses, including serum IgG levels, Th1 cytokine production (IFN-gamma), inflammatory markers (MIP-2), and immune cell infiltration (neutrophils, macrophages) following intranasal challenge.
Main Results:
- * Multivalent DNA vaccination via imEPT conferred the most robust protection against lethal P. aeruginosa pneumonia.
- * While whole-cell binding IgG levels were similar across groups, Th1-dominated multivalent IgG correlated strongly with protection.
- * Elevated bronchoalveolar MIP-2 and IFN-gamma levels, along with increased neutrophil and macrophage counts, were observed in protected mice.
Conclusions:
- * A multivalent DNA vaccine strategy, particularly when delivered via imEPT, is highly effective against P. aeruginosa.
- * Th1-biased immune responses are crucial for vaccine-induced protection against P. aeruginosa infection.
- * These findings support the potential clinical application of this multivalent DNA vaccine for P. aeruginosa prevention.
