Abstract
This review summarizes the authors’ studies in the past decade
aimed at developing a synthetic oligosaccharide-based glycoconjugate
vaccine to prevent a serious human disease caused by the Gram negative
bacterium Shigella dysenteriae type 1.
Starting from simple monosaccharides, oligosaccharides as large
as a 24 monosaccharide-containing linear polymer, were assembled.
Under suitable conditions, oligosaccharides containing 4 to 16 hexopyranose
residues were covalently attached to an immunogenic protein. The
serum response to the synthetic glycoconjugates depends, both on
the size of the oligosaccharides, and on the molar ratio of the
oligosaccharides to the carrier protein. Also reviewed are studies
of the fine specificities of the interaction between oligosaccharides
and anti-polysaccharide monoclonal antibodies as well as conformational
studies of the synthetic oligosaccharides.
1 Polysaccharide-Based Vaccines
1.1 Surface Polysaccharides of Bacteria
1.2 Immunologic Properties of Polysaccharides
1.3 Polysaccharide-Protein Conjugates
1.3.1 Methods for the Conjugation of Polysaccharides
to Proteins
1.3.2 Immunogenicity of Polysaccharide-Protein Conjugates
1.4 Synthetic Oligosaccharides Can be Superior to Natural Polysaccharides
for Glycoconjugate Vaccines
1.5 Potentials of the O-Specific Polysaccharides of Shigellae for Vaccine Development
2 Chemical Synthesis of Oligosaccharides Related to
theS.
dysenteriae Type 1
2.1 General Strategy
2.2 Synthesis of the Monosaccharide Building Blocks
2.2.1 The l -Rhamnose Moiety
2.2.2 The d -Galactose Moiety
2.2.3 The d -Glucosamine Synthons
2.3 Synthesis of a Complete Repeating Unit
2.4 Construction of Extended Oligosaccharides
2.5 The Lipophilic Protecting Group-Based Approach to
3 Covalent Attachment of the Oligosaccharides to Human
3.1 Conjugation through a Secondary Spacer, Using Reductive Amination
3.2 Conjugation through Diels-Alder Cycloaddition
Reactions
4 The Molecular Specificity of the Non-Covalent Binding
5 Conformational Studies
6 Immunogenicity of the Protein Conjugates of the Synthetic
7 Conclusions and Future Prospects
Key words
polysaccharide - oligosaccharides - monosaccharides - antibodies
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