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Outer membrane proteins of Pseudomonas aeruginosa as vaccine candidates
B von Specht1, B Knapp, K Hungerer
1Chirurgische Universitätsklinik, Chirurgische Forschung, Freiburg im Breisgau, Germany.
Abstract:
We tested the ability of the recombinant outer membrane proteins of Pseudomonas aeruginosa to serve as a protective vaccine against this Gram-negative pathogen in the presence of two main pathophysiological events leading to P. aeruginosa sepsis: (i) systemic infection during immunosuppression; and (ii) bacterial translocation. A hybrid vaccine was cloned which combined the protective epitopes of outer membrane protein F (OprF) and outer membrane protein I (OprI). This vaccine proved to be highly protective against an intraperitoneal challenge with P. aeruginosa in immunosuppressed mice. Oral immunization of mice with recombinant OprI expressing Salmonella dublin, induced s-IgA antibodies in the gut mucosa against OprI. These provided protection against translocation of P. aeruginosa in an immunosuppressed mouse model. To test whether OprI is effective in man, recombinant OprI was purified and used for the immunization of human volunteers. Immunization was tolerated well, and no side effects were observed. Antibody titers against OprI were measured in 90% of the volunteers after immunization.
Insights
This study developed a recombinant outer membrane protein vaccine for Pseudomonas aeruginosa sepsis. The vaccine showed protection in mice and was well-tolerated in human volunteers, indicating potential for preventing Gram-negative bacterial infections.
Area of Science:
- Immunology
- Microbiology
- Vaccine Development
Background:
- Pseudomonas aeruginosa sepsis is a significant threat, particularly in immunosuppressed individuals.
- Pathophysiological events like systemic infection and bacterial translocation complicate treatment.
- Outer membrane proteins (OMPs) are key targets for vaccines against Gram-negative pathogens.
Purpose of the Study:
- To evaluate the efficacy of a recombinant OMP-based vaccine against Pseudomonas aeruginosa.
- To assess vaccine protection in models of immunosuppression and bacterial translocation.
- To determine the safety and immunogenicity of OprI in human volunteers.
Main Methods:
- A hybrid vaccine combining outer membrane protein F (OprF) and outer membrane protein I (OprI) epitopes was constructed.
- Vaccine efficacy was tested in immunosuppressed mice challenged with P. aeruginosa.
- Oral immunization with OprI-expressing Salmonella dublin was used to induce mucosal immunity.
- Recombinant OprI was administered to human volunteers to assess safety and antibody response.
Main Results:
- The hybrid vaccine conferred significant protection against P. aeruginosa challenge in immunosuppressed mice.
- Oral immunization with OprI induced gut mucosal s-IgA antibodies, protecting against bacterial translocation.
- Recombinant OprI immunization in humans was well-tolerated with no observed side effects.
- Antibody titers against OprI were detected in 90% of immunized volunteers.
Conclusions:
- Recombinant outer membrane proteins of P. aeruginosa, specifically OprF and OprI, can serve as effective vaccine candidates.
- The developed vaccine strategies show promise in preventing P. aeruginosa sepsis under conditions of immunosuppression and translocation.
- OprI demonstrates safety and immunogenicity in humans, supporting its further development as a vaccine component.