A chimeric vaccine targeting Pseudomonas aeruginosa virulence factors protects mice against lethal infection
Fatemeh Korpi1, Gholamreza Irajian2, Fatemeh Forouhi1
1Department of Cell and Molecular Biology, Faculty of Basic Science, Islamic Azad University Shahre Qods Branch, Iran.
Abstract:
Pseudomonas aeruginosa is an important and hazardous nosocomial pathogen in respiratory tract infections and rapidly achieves antibiotic resistance, so it is necessary to develop an effective vaccine to combat the infection. The Type III secretion system (T3SS) protein P. aeruginosa V-antigen (PcrV), outer membrane protein F (OprF), and two kinds of flagellins (FlaA and FlaB) all play important roles in the pathogenesis of P. aeruginosa lung infection and its spread into deeper tissues. In a mouse acute pneumonia model, the protective effects of a chimer vaccine including PcrV, FlaA, FlaB, and OprF (PABF) protein were investigated. PABF immunization prompted robust opsonophagocytic titer of IgG antibodies and decreased bacterial burden, and improved survival afterward intranasal challenge with ten times 50% lethal doses (LD50) of P. aeruginosa strains, indicating its broad-spectrum immunity. Moreover, these findings showed a promise chimeric vaccine candidate to treat and control P. aeruginosa infections.
Insights
A new chimeric vaccine (PABF) combining P. aeruginosa V-antigen (PcrV), outer membrane protein F (OprF), and flagellins (FlaA, FlaB) shows promise against lung infections. Immunization reduced bacterial load and improved survival in a mouse model.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pseudomonas aeruginosa is a hazardous nosocomial pathogen causing respiratory tract infections.
- Rapid antibiotic resistance necessitates novel therapeutic strategies, including vaccines.
- Key virulence factors like PcrV, OprF, FlaA, and FlaB contribute to P. aeruginosa pathogenesis.
Purpose of the Study:
- To evaluate the protective efficacy of a chimeric vaccine (PABF) against Pseudomonas aeruginosa lung infection.
- To assess the immunogenicity and protective immune response induced by the PABF vaccine in a mouse model.
Main Methods:
- Development of a chimeric vaccine (PABF) comprising PcrV, OprF, FlaA, and FlaB proteins.
- Immunization of mice with the PABF vaccine.
- Intranasal challenge with a high dose of Pseudomonas aeruginosa strains.
- Assessment of bacterial burden, antibody titers, and survival rates.
Main Results:
- PABF immunization induced robust opsonophagocytic IgG antibody titers.
- Significant reduction in bacterial burden was observed in vaccinated mice.
- Improved survival rates were demonstrated after challenge with Pseudomonas aeruginosa.
- The vaccine conferred broad-spectrum immunity against P. aeruginosa strains.
Conclusions:
- The chimeric PABF vaccine candidate demonstrates significant protective efficacy against Pseudomonas aeruginosa lung infections.
- PABF vaccination elicits a strong immune response, reducing bacterial load and enhancing survival.
- This chimeric vaccine holds promise for the treatment and control of P. aeruginosa infections.
