Immunization of burn-patients with a Pseudomonas aeruginosa outer membrane protein vaccine elicits antibodies with protective efficacy

Lee, Na-Gyong; Jung, Sang Bo; Ahn, Bo Young; Kim, Young Hoon; Kim, Jeong-Jin; Kim, Dong-Kun; Kim, Ik-Sang; Yoon, Suk Min; Nam, Sung Woo; Kim, Hyun-Su; Park, Wan Je

doi:10.1016/s0264-410x(99)00479-x

Cited by 32 publications

(17 citation statements)

References 33 publications

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“…OMPs are more suitable as antigens than lipopolysaccharides, exopolysaccharides, or isolated flagella are for routine clinical use because of the safety and efficacy of OMPs. As one example, OprF has been well studied as a vaccine target because of the major porin (33), high antigenicity, and high homology among Pseudomonas strains (12,23,24). However, an immune response against OMPs involved in biofilm formation by P. aeruginosa has not been reported.…”

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Opr86 Is Essential for Viability and Is a Potential Candidate for a Protective Antigen against Biofilm Formation byPseudomonas aeruginosa

et al. 2008

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Pseudomonas aeruginosa is an opportunistic bacterial pathogen that is one of the most refractory to therapy when it forms biofilms in the airways of cystic fibrosis patients. To date, studies regarding the production of an immunogenic and protective antigen to inhibit biofilm formation by P. aeruginosa have been superficial. The previously uncharacterized outer membrane protein (OMP) Opr86 (PA3648) of P. aeruginosa is a member of the Omp85 family, of which homologs have been found in all gram-negative bacteria. Here we verify the availability of Opr86 as a protective antigen to inhibit biofilm formation by P. aeruginosa PAO1 and several other isolates. A mutant was constructed in which Opr86 expression could be switched on or off through a tac promoter-controlled opr86 gene. The result, consistent with previous Omp85 studies, showed that Opr86 is essential for viability and plays a role in OMP assembly. Depletion of Opr86 resulted in streptococci-like morphological changes and liberation of excess membrane vesicles. A polyclonal antibody against Opr86 which showed reactivity to PAO1 cells was obtained. The antibody inhibited biofilm formation by PAO1 and the other clinical strains tested. Closer examination of early attachment revealed that cells treated with the antibody were unable to attach to the surface. Our data suggest that Opr86 is a critical OMP and a potential candidate as a protective antigen against biofilm formation by P. aeruginosa.Pseudomonas aeruginosa is a major opportunistic pathogen responsible for many human diseases, such as cystic fibrosis and nosocomial infections such as bacteremia and pneumonia in immunocompromised hosts. Control of infection frequently proves difficult due to high levels of antibiotic resistance (44) and the fact that the organism is known to exist in the body in a biofilm state, which confers even more resistance (6, 26). Biofilms are adherent aggregates of bacterial cells that form matrix-enclosed, complex, and organized communities on biotic and abiotic surfaces (18,19,46). Bacteria in biofilms are resistant to antibiotics (8,27) and less conspicuous to the immune system (6, 14).Host immunological defenses prevent human pathogens from infecting particular areas of the body, and this is well characterized in pathology, immunology, and bacteriology. In the last decade, outer membrane proteins (OMPs) belonging to the Omp85 family have been identified as antigens in pathogenesis and immunity. For example, several studies of Haemophilus influenzae infection using animal models demonstrated that 85-kDa OMP D15 confers protection against homologous and heterologous strains (25,52). Similarly, Oma87 of Pasteurella multocida has been shown to elicit protection in an animal model of infection (41). D15 and Oma87, as well as Tp92 of Treponema pallidum, Omp85 of Neisseria meningitidis, and YaeT of Escherichia coli, are members of the Omp85 family, and Omp85 homologs are highly conserved among gram-negative bacteria (5, 43, 49). Omp85/YaeT has recently been well characterized in ...

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“…aeruginosa OMPs have been studied as candidates for vaccine antigens in the form of purified OM preparations (22,24), isolated OMPs (38, 48), or protein fusions (1, 21). OMPs are more suitable as antigens than lipopolysaccharides, exopolysaccharides, or isolated flagella are for routine clinical use because of the safety and efficacy of OMPs.…”

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Opr86 Is Essential for Viability and Is a Potential Candidate for a Protective Antigen against Biofilm Formation byPseudomonas aeruginosa

et al. 2008

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“…Vaccination with outer membrane protein antigens has been shown to be efficacious against P. aeruginosa infection in a number of studies using killed whole cells (9), purified outer membrane preparations (32,33), isolated outer membrane proteins (18,20,39,53), protein fusions (38), or synthetic peptides representing protective epitopes (22,23). The P. aeruginosa major constitutive porin protein, OprF, which has previously been shown to be antigenic (3,20,25) and has high homology among Pseudomonas strains (18,34,40), was chosen as a vaccine target.…”

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Protection againstPseudomonas aeruginosaChronic Lung Infection in Mice by Genetic Immunization against Outer Membrane Protein F (OprF) ofP. aeruginosa

et al. 2001

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The Pseudomonas aeruginosa major constitutive outer membrane porin protein OprF, which has previously been shown to be a protective antigen, was targeted as a DNA vaccine candidate. The oprF gene was cloned into plasmid vector pVR1020, and the plasmid vaccines were delivered to mice by biolistic (gene gun) intradermal inoculation. Antibody titers in antisera from immunized mice were determined by enzyme-linked immunosorbent assay, and the elicited antibodies were shown to be specifically reactive to OprF by immunoblotting. The immunoglobulin G (IgG) immune response was predominantly of the IgG1 isotype. Sera from DNA vaccineimmunized mice had significantly greater opsonic activity in opsonophagocytic assays than did sera from control mice. Following the initial immunization and two consecutive boosts, each at 2-week intervals, protection was demonstrated in a mouse model of chronic pulmonary infection by P. aeruginosa. Eight days postchallenge, both lungs were removed and examined. A significant reduction in the presence of severe macroscopic lesions, as well as in the number of bacteria present in the lungs, was seen. Based on these findings, genetic immunization with oprF has potential for development as a vaccine to protect humans against infection by P. aeruginosa.Pseudomonas aeruginosa, an opportunistic pathogen, is a leading cause of life-threatening infections in immunocompromised individuals. It is an etiological agent of bacteremia, urinary tract infections, and pneumonia in such patients. The mortality from bacteremia and pneumonia caused by P. aeruginosa infections can exceed 50%. Each year, over two million patients develop hospital-associated infections, and an estimated 88,000 patients die as a result.

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“…There is no reliable P. aeruginosa vaccine produced so far, although many attempts have been made [10,14,24,25]. In 1984, Gilleland et al used the porin of P. aeruginosa as a protective vaccine in mice [10].…”

Section: Discussionmentioning

confidence: 99%

“…Different antigens of P. aeruginosa, such as the outer membrane proteins (OMPs), LPS, toxins, pilli and flagella, have been investigated as possible targets for the development of vaccines. Vaccination with outer membrane protein antigens has been shown to be efficacious against P. aeruginosa infection in a number of studies using killed whole cells [9], isolated outer membrane proteins [10][11][12][13] and purified outer membrane preparations [14]. The P. aeruginosa major constitutive porin protein, OMP-F, which has previously been shown to be antigenic [10,15] and has high homology among Pseudomonas strains [12,16], was also chosen as a vaccine target [17].…”

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confidence: 99%

Immunological evaluation of OMP-F of native Iranian Pseudomonas aeruginosa as a protective vaccine

Ahmadi

Tabaraie

Maleknia

et al. 2012

J Infect Dev Ctries

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Introduction: This study involved 300 Pseudomonas aeruginosa strains isolated from patients admitted in four Tehran hospitals. Using standard O-specific typing sera, they were all grouped into 16 strains out of 17 known P. aeruginosa. The strains were lyophilized and each was given a code according to the Collection of Standard Bacteria, Pasteur Institute of Iran (CSBPI) for further investigations. Methodology: Among all clinical samples, CSBPI: 16-190 was the most prevalent P. aeruginosa serotype which showed a high agglutination titer (4+, 320) against homologous O-specific typing sera. This serotype was selected for extraction of P. aeruginosa major outer membrane vesicles (OMP-F). OMP-F vesicles were extracted and purified according to the Deoxycholate Ultracentrifuge Differentiation Technique. Purity and molecular weight of OMP-F were determined by SDS-PAGE and the ability of OMP-F vesicles to induce high titers of antibody in rabbit, which was shown as a sharp antibody-antigen precipitation line in the agarose gel immune-diffusion technique. Results: Passive immunization of mice with anti-rabbit OMP-F antisera induced a high level of protection when the mice were postchallenged with 2×LD50 of live P. aeruginosa CSBPI: . Furthermore, active immunization of mice with 50 µg of OMP-F could protect mice against 2×LD50 of live homologous (100% protection) and 15 heterologous native Iranian P. aeruginosa serotypes with 50-100% level of protection. Conclusions: These investigations indicate that purified OMP-F of CSBPI: 16-190 can be regarded as a safe protective immunogen in vaccinothrapy against all P. aeruginosaimmunotype isolated in Iran.

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Immunization of burn-patients with a Pseudomonas aeruginosa outer membrane protein vaccine elicits antibodies with protective efficacy

Cited by 32 publications

References 33 publications

Opr86 Is Essential for Viability and Is a Potential Candidate for a Protective Antigen against Biofilm Formation byPseudomonas aeruginosa

Opr86 Is Essential for Viability and Is a Potential Candidate for a Protective Antigen against Biofilm Formation byPseudomonas aeruginosa

Protection againstPseudomonas aeruginosaChronic Lung Infection in Mice by Genetic Immunization against Outer Membrane Protein F (OprF) ofP. aeruginosa

Immunological evaluation of OMP-F of native Iranian Pseudomonas aeruginosa as a protective vaccine

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