A recombinant hybrid outer membrane protein for vaccination against Pseudomonas aeruginosa

Knapp, Bernhard; Hundt, Erika; Lenz, Uwe; Hungerer, Klaus-Dieter; Gabelsberger, Josef; Domdey, Horst; Mansouri, Erfan; Li, Yuanyi; Specht, Bernd-Ulrich von

doi:10.1016/s0264-410x(98)00420-4

Cited by 33 publications

(29 citation statements)

References 10 publications

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“…OprF is a major outer membrane protein in Pseudomonas aeruginosa that has been studied extensively due to its proposed utility as a vaccine component, its role in antimicrobial drug resistance, and its porin function (3,6,7,13,20). It has been shown to be required for cell growth in low-osmolarity medium and for the maintenance of cell shape (21).…”

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confidence: 99%

The Amino Terminus of Pseudomonas aeruginosa Outer Membrane Protein OprF Forms Channels in Lipid Bilayer Membranes: Correlation with a Three-Dimensional Model

2000

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Pseudomonas aeruginosa OprF forms 0.36-nS channels and, rarely, 2-to 5-nS channels in lipid bilayer membranes. We show that a protein comprising only the N-terminal 162-amino-acid domain of OprF formed the smaller, but not the larger, channels in lipid bilayers. Circular dichroism spectroscopy indicated that this protein folds into a ␤-sheet-rich structure, and three-dimensional comparative modeling revealed that it shares significant structural similarity with the amino terminus of the orthologous protein Escherichia coli OmpA, which has been shown to form a ␤-barrel. OprF and OmpA share only 15% identity in this domain, yet these results support the utility of modeling such widely divergent ␤-barrel domains in three dimensions in order to reveal similarities not readily apparent through primary sequence comparisons. The model is used to further hypothesize why porin activity differs for the N-terminal domains of OprF and OmpA.

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The Amino Terminus of Pseudomonas aeruginosa Outer Membrane Protein OprF Forms Channels in Lipid Bilayer Membranes: Correlation with a Three-Dimensional Model

2000

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“…Although vaccination with P. aeruginosa lipopolysaccharide was effective in several animal models and led to the production of highly opsonic antibodies, the efficacy in human trials was limited by antigenic diversity of O antigens among P. aeruginosa isolates (11). Since flagellin, OprI, and OprF exhibit conserved amino acid sequences, more recent studies have focused on these proteins as potential vaccine antigens (14,26,31,67,68).…”

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confidence: 99%

“…Although large amounts of this protein were required for an optimal response, immunization with an OprF-OprI fusion protein resulted in a 95-fold increase in the 50% lethal dose for mice. A subsequent study in burn patients revealed that an OprF-OprI fusion protein was immunogenic and well tolerated (26,31).…”

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A Fusion Protein Vaccine Containing OprF Epitope 8, OprI, and Type A and B Flagellins Promotes Enhanced Clearance of Nonmucoid Pseudomonas aeruginosa

Weimer

Kock

et al. 2009

Infect Immun

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“…In the case of a pVR1020/oprF vaccine specifically, additional vaccine components, such as P. aeruginosa PcrV (43), outer membrane protein I (30,53), or elastase epitopes (46), all of which have previously been shown to be antigenic, might be combined with oprF to augment the final vaccine's effectiveness. Moreover, the effectiveness of the final vaccine in humans may depend on determining the optimal vaccination protocol.…”

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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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A recombinant hybrid outer membrane protein for vaccination against Pseudomonas aeruginosa

Cited by 33 publications

References 10 publications

The Amino Terminus of Pseudomonas aeruginosa Outer Membrane Protein OprF Forms Channels in Lipid Bilayer Membranes: Correlation with a Three-Dimensional Model

The Amino Terminus of Pseudomonas aeruginosa Outer Membrane Protein OprF Forms Channels in Lipid Bilayer Membranes: Correlation with a Three-Dimensional Model

A Fusion Protein Vaccine Containing OprF Epitope 8, OprI, and Type A and B Flagellins Promotes Enhanced Clearance of Nonmucoid Pseudomonas aeruginosa

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

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