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Development of a synthetic peptide v...

Kao, Daniel Joseph.

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Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection./
Author:	Kao, Daniel Joseph.
Description:	261 p.
Notes:	Adviser: Robert S. Hodges.
Contained By:	Dissertation Abstracts International68-08B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3277182
ISBN:	9780549190394

Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection.
Kao, Daniel Joseph.

Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection. - 261 p.

Adviser: Robert S. Hodges.

Thesis (Ph.D.)--University of Colorado Health Sciences Center, 2007.

The type IV pilus is an adhesion that is critical in the pathogenesis of Pseudomonas aeruginosa infection and a good candidate for development of an anti-adhesin vaccine. The receptor binding domain of the type IV pilus resides in a C-terminal disulfide loop of the pilin subunit and is responsible for mediating adhesion to eukaryotic epithelia. In this study, a synthetic peptide vaccine targeting the receptor binding domain has been validated through analysis of polyclonal sera raised in mice and rabbits. We have shown that antibodies raised against the peptide immunogen domain are present in higher concentration and have higher affinity for the receptor binding domain of the intact pilin protein than antibodies raised against the pilin protein itself. We have also characterized a consensus sequence peptide immunogen, termed Cs1, which has been designed to generate an immune response that provides protection against infection by multiple strains of P. aeruginosa. We have shown that the Cs1 peptide can induce the production of antibodies that are cross-reactive against the PAK and PAO pilin proteins. The high resolution X-ray crystal structure of the Cs1 sequence in the context of an intact pilin protein was determined to gain insight into the structural basis for the novel immunological activity that was observed. There were few differences in the backbone conformation between the Cs1 structure and the known structures of native strain pilins. Based on these findings, we have proposed that the cross-reactivity of the immune response to Cs1 is modulated by the side chain composition of the solvent-exposed residues of the pilin receptor binding domain. Additionally, one of the consensus sequence substitutions may be important for stabilizing the secondary structure of the receptor binding domain, while the other substitution may be important for determining antibody specificity. In summary, we have demonstrated that a synthetic peptide vaccine targeting the type IV pilus of P. aeruginosa presents a number of advantages over using an intact pilin protein and have shown how modification of the peptide immunogen may modulate the antibody response to create a cross-protective vaccine.

ISBN: 9780549190394Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection.
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100 1 $a Kao, Daniel Joseph. $3 1262917
245 1 0 $a Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas aeruginosa infection.
300 $a 261 p.
500 $a Adviser: Robert S. Hodges.
500 $a Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5159.
502 $a Thesis (Ph.D.)--University of Colorado Health Sciences Center, 2007.
520 $a The type IV pilus is an adhesion that is critical in the pathogenesis of Pseudomonas aeruginosa infection and a good candidate for development of an anti-adhesin vaccine. The receptor binding domain of the type IV pilus resides in a C-terminal disulfide loop of the pilin subunit and is responsible for mediating adhesion to eukaryotic epithelia. In this study, a synthetic peptide vaccine targeting the receptor binding domain has been validated through analysis of polyclonal sera raised in mice and rabbits. We have shown that antibodies raised against the peptide immunogen domain are present in higher concentration and have higher affinity for the receptor binding domain of the intact pilin protein than antibodies raised against the pilin protein itself. We have also characterized a consensus sequence peptide immunogen, termed Cs1, which has been designed to generate an immune response that provides protection against infection by multiple strains of P. aeruginosa. We have shown that the Cs1 peptide can induce the production of antibodies that are cross-reactive against the PAK and PAO pilin proteins. The high resolution X-ray crystal structure of the Cs1 sequence in the context of an intact pilin protein was determined to gain insight into the structural basis for the novel immunological activity that was observed. There were few differences in the backbone conformation between the Cs1 structure and the known structures of native strain pilins. Based on these findings, we have proposed that the cross-reactivity of the immune response to Cs1 is modulated by the side chain composition of the solvent-exposed residues of the pilin receptor binding domain. Additionally, one of the consensus sequence substitutions may be important for stabilizing the secondary structure of the receptor binding domain, while the other substitution may be important for determining antibody specificity. In summary, we have demonstrated that a synthetic peptide vaccine targeting the type IV pilus of P. aeruginosa presents a number of advantages over using an intact pilin protein and have shown how modification of the peptide immunogen may modulate the antibody response to create a cross-protective vaccine.
590 $a School code: 0831.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Health Sciences, Pharmacology. $3 1017717
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792 $a 2007
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