Synthesis, characterization, and immunogenicity of O-specific polysaccharide based glycan vaccine against Salmonella typhimurium
Date Issued
2011-06-28
Date
2011-06-28
Author(s)
陳明正
Chen, Ming-Cheng
Abstract
The synthesis of glycan conjugate is the critical issue in the glycan vaccinology. Traditionally, an immunogen is composed of protein or peptide fragments, but using the highly conservative glycan on the surface of pathogen (e.g. lipopolysaccharide, LPS) or tumor cell (e.g. Global H) as the immunogen has illuminated another direction in vaccine research. For Gram-negative bacteria, the 3-deoxy-D-manno-octulosonic acid (Kdo) is an attractive target for glycan immunogen synthesis. It is highly conservatively at the terminal of O-specific polysaccharide of LPS, and the derivatization from Kdo retains the immunogenicity for immune cell recognition. However, there is no efficient method has been developed for the synthesis of Kdo-derivatized glycan conjugates.
In our study, a new method for the construction of glycan conjugate from Kdo is developed. This method is site-specific and reacts under mild acid conditions between O-specific polysaccharide and diamine linker. Utilizing the LPS of E. coli as a model, we have successfully synthesized the glycan conjugates and evaluated its immunogenicity. In another part, we target Salmonella typhimurium, which is a highly pathogenic Gram-negative bacterium worldwide. After more than thirty years’ investigation, there still lacks an efficient vaccine for S. typhimurium prevention. To further apply our conjugation method, the glycan immunogens were synthesized from the immunogenic fractions of LPS in S. typhimurium. The corresponding immunization experiment is in progress. Our strategy might promise a new approach for the development of S. typhimurium glycan vaccine.
Subjects
glycan vaccine
kdo
lipopolysaccharide
o-phenylenediamines
Salmonella
typhimurium
SDGs
Type
thesis
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