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Development of Vaccine Candidates Against Emerging Bacteria via Chemical Syntheses of Antigens.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Development of Vaccine Candidates Against Emerging Bacteria via Chemical Syntheses of Antigens./
Author:	Shen, Dacheng.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	159 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-07, Section: B.
Contained By:	Dissertations Abstracts International82-07B.
Subject:	Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28120205
ISBN:	9798698512585

Development of Vaccine Candidates Against Emerging Bacteria via Chemical Syntheses of Antigens.
Shen, Dacheng.

Development of Vaccine Candidates Against Emerging Bacteria via Chemical Syntheses of Antigens. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 159 p.

Source: Dissertations Abstracts International, Volume: 82-07, Section: B.

Thesis (D.Sc.)--Freie Universitaet Berlin (Germany), 2019.

This item must not be sold to any third party vendors.

Bacterial infections have long been an ever-emerging problem with the appearance of antibiotic resistant bacteria which is deteriorating with the misuse and abuse of antibiotics. As infections of these emerging bacteria can hardly be treated, we are seeking a protective method to fight bacteria by the development of glycoconjugate vaccines. Chemical syntheses to obtain pure structures of the target antigens are essential for further glycobiology and immunity studies.Chapter 2 describes my work on the development of the vaccine candidates against Klebsiella pneumoniae sequence type 258 (KPST258). This "super bug" can produce K. pneumoniae carbapenemases (KPC) to protect it from almost all the available antibiotics. I designed and synthesized the two structures, trisaccharide 2-1 containing one repeating unit and hexasaccharide 2-2 containing two repeating units. (Figure 1) The repeating unit contains a C3, C4-branched galactose with a galactofuranose connected to its C3 position. This kind of oligosaccharide had never been well studied and chemical synthesis to obtain such a dense branched structure in the hexasaccharide bridged via a galactofuranose at C1 and C3 positions has never been reported either. Each oligosaccharide carries an amino linker, making it possible for further glycan array tests or conjugation for immunization and other biological evaluations. In collaboration with Bruna M. S. Seco, we performed glycan array tests and found sera from infected patients contained antibodies against both 2-1 and 2-2. The glycans were further conjugated to carrier protein CRM197 for immunization tests. CRM197-2-2 triggered a robust immune response in rabbits, indicating that it is a promising vaccine candidate against Klebsiella pneumoniae ST258.Chapter 3 describes my work regarding an important swine pathogen Streptococcus suis. This bacterium exists in almost every pig farm around the world. Huge economic loss has been caused every year in swine industry and humans can also be infected. We became interested in S. suis serotypes 3 and 18, and the antigens I have been developing contain rare and interesting bacillosamine residues. Chemical modification of L-Bacillosamine has never been reported before, so I did some pioneering study on this sugar structure, hoping to achieve a better understanding of its properties and provide some reference for possible future study. The experience with monosaccharide modifications can be applied in D-bacillosamine modification for the synthesis of S. suis antigens. The final antigens are not finished yet, but most of the synthetic problems have been solved including the most complicated parts to establish the synthesis routes to the target molecules. The last stage of the antigen syntheses and immunological evaluations will be investigated in the future.

ISBN: 9798698512585Subjects--Topical Terms:

536250
Microbiology.
Subjects--Index Terms:

Vaccine

Development of Vaccine Candidates Against Emerging Bacteria via Chemical Syntheses of Antigens.
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500 $a Source: Dissertations Abstracts International, Volume: 82-07, Section: B.
500 $a Advisor: Seeberger, Peter H.
502 $a Thesis (D.Sc.)--Freie Universitaet Berlin (Germany), 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Bacterial infections have long been an ever-emerging problem with the appearance of antibiotic resistant bacteria which is deteriorating with the misuse and abuse of antibiotics. As infections of these emerging bacteria can hardly be treated, we are seeking a protective method to fight bacteria by the development of glycoconjugate vaccines. Chemical syntheses to obtain pure structures of the target antigens are essential for further glycobiology and immunity studies.Chapter 2 describes my work on the development of the vaccine candidates against Klebsiella pneumoniae sequence type 258 (KPST258). This "super bug" can produce K. pneumoniae carbapenemases (KPC) to protect it from almost all the available antibiotics. I designed and synthesized the two structures, trisaccharide 2-1 containing one repeating unit and hexasaccharide 2-2 containing two repeating units. (Figure 1) The repeating unit contains a C3, C4-branched galactose with a galactofuranose connected to its C3 position. This kind of oligosaccharide had never been well studied and chemical synthesis to obtain such a dense branched structure in the hexasaccharide bridged via a galactofuranose at C1 and C3 positions has never been reported either. Each oligosaccharide carries an amino linker, making it possible for further glycan array tests or conjugation for immunization and other biological evaluations. In collaboration with Bruna M. S. Seco, we performed glycan array tests and found sera from infected patients contained antibodies against both 2-1 and 2-2. The glycans were further conjugated to carrier protein CRM197 for immunization tests. CRM197-2-2 triggered a robust immune response in rabbits, indicating that it is a promising vaccine candidate against Klebsiella pneumoniae ST258.Chapter 3 describes my work regarding an important swine pathogen Streptococcus suis. This bacterium exists in almost every pig farm around the world. Huge economic loss has been caused every year in swine industry and humans can also be infected. We became interested in S. suis serotypes 3 and 18, and the antigens I have been developing contain rare and interesting bacillosamine residues. Chemical modification of L-Bacillosamine has never been reported before, so I did some pioneering study on this sugar structure, hoping to achieve a better understanding of its properties and provide some reference for possible future study. The experience with monosaccharide modifications can be applied in D-bacillosamine modification for the synthesis of S. suis antigens. The final antigens are not finished yet, but most of the synthetic problems have been solved including the most complicated parts to establish the synthesis routes to the target molecules. The last stage of the antigen syntheses and immunological evaluations will be investigated in the future.
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650 4 $a Pharmacology. $3 634543
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650 4 $a Pharmaceutical sciences. $3 3173021
650 4 $a Biochemistry. $3 518028
653 $a Vaccine
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653 $a Chemical syntheses
653 $a Antigen
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