Outer membrane protein F preparation of Pseudomonas aeruginosa as a vaccine against chronic pulmonary infection with heterologous immunotype strains in a rat model

Gilleland, H. E.; Gilleland, Linda B.; Matthews-Greer, Janice

doi:10.1128/iai.56.5.1017-1022.1988

Cited by 66 publications

(44 citation statements)

References 25 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our laboratory has been examining the use of protein F (OprF) from the outer membrane of P. aeruginosa as a protective vaccine. We have used a number of rodent models of infection [24,27,31,39,40] with P. aeruginosa to demonstrate the protective e⁄cacy of protein F in various forms. These include the use of the puri¢ed protein [27,31,39,41], synthetic peptides coupled to a carrier protein [26,40,42], a chimeric virus engineered to contain one or two epitopes of protein F within a viral surface protein Table 5 Protection a¡orded upon passive administration of the various antisera…”

Section: Discussionmentioning

confidence: 99%

“…Eight days after the challenge, protection a¡orded to the immunized mice by the DNA vaccine was assessed by two methods. First, the lungs were examined macroscopically for the presence of lesions [24,31,32]. Lesions were scored as 0 to 4+ as follows : 0, absence of any macroscopic lesion ; 1+, presence of one or two small lesions not exceeding 1 mm in diameter ; 2+, presence of three or more small lesions not exceeding 1 mm in diameter; 3+, presence of a medium lesion 2^5 mm in diameter ; 4+ presence of a large lesion exceeding 5 mm in diameter.…”

Section: Assay For Immunoprotection Upon Active Immunizationmentioning

confidence: 99%

“…Lesions scored as 2+ to 4+ were considered to be severe lesions. Second, bacterial quantitation of the number of P. aeruginosa present in the lungs was performed as described previously [24,31,32]. Brie£y, both lungs were aseptically removed and homogenized in a 1:10 (w/v) dilution of sterile saline with a tissue grinder.…”

Section: Assay For Immunoprotection Upon Active Immunizationmentioning

confidence: 99%

“…Each strategy (prime-boost approach of priming immunizations with pVR1020/oprF DNA followed by boost with the chimeric HG10-11 virus or approach of immunizations with pVR1020/oprF/I DNA) yielded a level of protective e⁄cacy that compares favorably with that previously seen using protein F itself puri¢ed from the outer membrane of P. aeruginosa. A compilation of data from three previously published studies [31,41,49] using protein F as a vaccine in the rodent chronic pulmonary infection model revealed that, compared to control-immunized animals which had severe lesions present in the lungs of 71.6% (139/194) of the group with only 23% (14/60) having sterile lungs, protein F-immunized animals had 28.6% (52/ 182) with severe lesions present in the lungs and 59% (35/ 59) with sterile lungs upon bacterial quantitation of the number of P. aeruginosa present in the lungs. The results from the present study (Tables 3 and 4) indicate that a DNA vaccine holds promise for providing protection at an equivalent level to that provided by the puri¢ed protein itself.…”

Section: Serummentioning

confidence: 99%

See 3 more Smart Citations

Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa

Price

2002

FEMS Immunology and Medical Microbiology

View full text Add to dashboard Cite

The outer membrane protein F gene (oprF) of Pseudomonas aeruginosa was recently shown by us to protect mice from P. aeruginosa chronic pulmonary infection when used as a DNA vaccine administered by three biolistic (gene gun) intradermal inoculations given at 2-week intervals. In the present study, we used two different strategies to improve the protective efficacy of the DNA vaccine. In the first strategy, mice were primed with two biolistic intradermal inoculations with the oprF vaccine and then were given a final intramuscular booster immunization containing either a synthetic peptide-keyhole limpet hemocyanin (KLH) conjugate or a chimeric influenza virus. Both the synthetic peptide conjugate and the chimeric virus contained peptide 10, a previously identified immunoprotective epitope of protein F. The second strategy involved the addition of a second outer membrane protein to the vaccine. DNA encoding a fusion protein comprised of the C-terminal half of protein F fused to OprI was administered by three biolistic intradermal inoculations. Challenge with P. aeruginosa in a chronic pulmonary infection model demonstrated that boosting with the chimeric virus (but not with peptide-KLH) or adding oprI to the DNA vaccine significantly enhanced protection as compared to that afforded by the oprF vaccine given alone. Thus, both strategies appear to augment the protection afforded by an oprF-only DNA vaccine.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Assay For Immunoprotection Upon Active Immunizationmentioning

confidence: 99%

Section: Assay For Immunoprotection Upon Active Immunizationmentioning

confidence: 99%

Section: Serummentioning

confidence: 99%

See 2 more Smart Citations

Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa

Price

2002

FEMS Immunology and Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…Early on we surveyed the protective abilities of a variety of puri¢ed OM proteins (D2, E, F, G, and H), reaching the conclusion that protein F had the greatest vaccine potential [2]. Protein F puri¢ed from the OM of P. aeruginosa was shown to a¡ord sig-ni¢cant protection in rodent models of systemic infection [3], burned mice [4], and chronic pulmonary infection [5]. Recombinant protein F puri¢ed from Escherichia coli was shown to retain vaccine e¤cacy in the burned mouse [2] and the rat chronic pulmonary infection [6] models.…”

Section: Introductionmentioning

confidence: 99%

Chimeric animal and plant viruses expressing epitopes of outer membrane protein F as a combined vaccine against Pseudomonas aeruginosa lung infection

Gilleland

2000

FEMS Immunology and Medical Microbiology

View full text Add to dashboard Cite

Outer membrane protein F of Pseudomonas aeruginosa has vaccine efficacy against infection by P. aeruginosa as demonstrated in a variety of animal models. Through the use of synthetic peptides, three surface-exposed epitopes have been identified. These are called peptides 9 (aa 261-274 in the mature F protein, TDAYNQKLSERRAN), 10 (aa 305-318, NATAEGRAINRRVE), and 18 (aa 282-295, NEYGVEGGRVNAVG). Both the peptide 9 and 10 epitopes are protective when administered as a vaccine. In order to develop a vaccine that is suitable for use in humans, including infants with cystic fibrosis, the use of viral vector systems to present the protective epitopes has been investigated. An 11-amino acid portion of epitope 10 (AEGRAINRRVE) was successfully inserted into the antigenic B site of the hemagglutinin on the surface of influenza virus. This chimeric influenza virus protects against challenge with P. aeruginosa in the mouse model of chronic pulmonary infection. Attempts to derive a chimeric influenza virus carrying epitope 9 have been unsuccessful. A chimeric plant virus, cowpea mosaic virus (CPMV), with epitopes 18 and 10 expressed in tandem on the large coat protein subunit (CPMV-PAE5) was found to elicit antibodies that reacted exclusively with the 10 epitope and not with epitope 18. Use of this chimeric virus as a vaccine afforded protection against challenge with P. aeruginosa in the mouse model of chronic pulmonary infection. Chimeric CPMVs with a single peptide containing epitopes 9 and 18 expressed on either of the coat proteins are in the process of being evaluated. Epitope 9 was successfully expressed on the coat protein of tobacco mosaic virus (TMV), and this chimeric virus is protective when used as a vaccine in the mouse model of chronic pulmonary infection. However, initial attempts to express epitope 10 on the coat protein of TMV have been unsuccessful. Efforts are continuing to construct chimeric viruses that express both the 9 and 10 epitopes in the same virus vector system. Ideally, the use of a vaccine containing two epitopes of protein F is desirable in order to greatly reduce the likelihood of selecting a variant of P. aeruginosa that escapes protective antibodies in immunized humans via a mutation in a single epitope within protein F. When the chimeric influenza virus containing epitope 10 and the chimeric TMV containing epitope 9 were given together as a combined vaccine, the immunized mice produced antibodies directed toward both epitopes 9 and 10. The combined vaccine afforded protection against challenge with P. aeruginosa in the chronic pulmonary infection model at approximately the same level of efficacy as provided by the individual chimeric virus vaccines. These results prove in principle that a combined chimeric viral vaccine presenting both epitopes 9 and 10 of protein F has vaccine potential warranting continued development into a vaccine for use in humans.

show abstract

DNA Vaccines Against Bacterial Pathogens

Chambers¹,

Vordermeier²,

Hewinson³

et al. 2003

DNA Vaccines

View full text Add to dashboard Cite

Outer membrane protein F preparation of Pseudomonas aeruginosa as a vaccine against chronic pulmonary infection with heterologous immunotype strains in a rat model

Cited by 66 publications

References 25 publications

Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa

Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa

Chimeric animal and plant viruses expressing epitopes of outer membrane protein F as a combined vaccine against Pseudomonas aeruginosa lung infection

DNA Vaccines Against Bacterial Pathogens

Contact Info

Product

Resources

About