2004 Fiscal Year Final Research Report Summary
Development of oligosaccharide conjugates that could be potentially utilized as vaccines against pathogenic Gram-negative bacteria
| Project/Area Number |
14360207
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | Tottori University |
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Principal Investigator |
YAMASAKI Ryohei Tottori University, Faculty of Agriculture, Professor, 農学部, 教授 (80273887)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIYANAGI Tsuyoshi Tottori University, Faculty of Agriculture, Lecturer, 農学部, 講師 (00302240)
ESUMI Yasuaki The Institute of Physical and Chemical Research, Senior Research Associate, 分子構造解析室, 先任技師 (70087500)
KOMASE Katsuhiro Kitasato University, Research Center for Biologicals, Head of Development Division, 生物製剤研究所・開発研究部門, 部門長(研究職) (80215384)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Lipooligosaccharide / Lipopolysaccharide / Oligosaccharide / Vaccine / Gram-negative bacteria / Human antibodies / Epitope |
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| Research Abstract |
The object of this research is to study the possibility to develop carbohydrate vaccines t against pathogenic Gram-negative bacteria. We accomplished the following during the funding period.
1)Synthesis of branched core oligosaccharide(OS) expressed in 15253 LOS and OS conjugates. 15253 We developed a new heptose (Hep) intermediate, 3-O-silyl-Hep, for the synthesis of the core OS. By utilizing the Hep intermediate, we constructed the following branched core OS : the 2,3-,3,4-branched, and 2,3;3,4-dibranched structures. We also developed a basic strategy to synthesize OS conjugates using a model OS. Finally, we synthesize a-spacer KDO side by stereoselective anomeric O-acylation.
2)Analysis of antibodies specific for the core OS and the immunogenicity of a model OS conjugate. We characterized several antibodies that are specific for the core OS and showed that those core OS structures are immunogenic in humans for the first time, We also developed a sensitive western blot assay that would allow the detection of LOS (femt mol level) with lower concentration of antibodies and used this assay for the analysis of specificities of the above antibodies and anti-sera raised using the model OS conjugate.
Thus, we established a methodology for the synthesis of branched core OS and have shown that such core OS can be utilized for the development of vaccines against pathogenic Gram-negative bacteria.
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Research Products
(14 results)
