Discovery of Semi- and Fully-Synthetic Carbohydrate Vaccines Against Bacterial Infections Using a Medicinal Chemistry Approach

The glycocalyx, a thick layer of carbohydrates, surrounds the cell wall of most bacterial and parasitic pathogens. Recognition of these unique glycans by the human immune system results in destruction of the invaders. To elicit a protective immune response, polysaccharides either isolated from the b...

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Bibliographic Details
Published in:Chemical reviews 2021-04, Vol.121 (7), p.3598
Main Author: Seeberger, Peter H
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial diseases
Bacterial infections
Bacterial Infections - prevention & control
Carbohydrates
Chemistry
Clostridioides difficile
Glycan
Glycocalyx - chemistry
Glycoconjugates - chemistry
Humans
Immune response
Immune system
Infections
Klebsiella
Klebsiella pneumoniae
Parasitic diseases
Pharmaceutical sciences
Pharmaceuticals
Polysaccharides
Polysaccharides - chemistry
Saccharides
Small Molecule Libraries - chemistry
Streptococcus infections
Streptococcus pneumoniae
Structure-Activity Relationship
Vaccines
Vaccines, Conjugate - chemistry
Vaccines, Conjugate - pharmacology
Vaccines, Synthetic - chemistry
Vaccines, Synthetic - pharmacology
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Summary:The glycocalyx, a thick layer of carbohydrates, surrounds the cell wall of most bacterial and parasitic pathogens. Recognition of these unique glycans by the human immune system results in destruction of the invaders. To elicit a protective immune response, polysaccharides either isolated from the bacterial cell surface or conjugated with a carrier protein, for T-cell help, are administered. Conjugate vaccines based on isolated carbohydrates currently protect millions of people against , type b, and infections. Active pharmaceutical ingredients (APIs) are increasingly discovered by medicinal chemistry and synthetic in origin, rather than isolated from natural sources. Converting vaccines from biologicals to pharmaceuticals requires a fundamental understanding of how the human immune system recognizes carbohydrates and could now be realized. To illustrate the chemistry-based approach to vaccine discovery, I summarize efforts focusing on synthetic glycan-based medicinal chemistry to understand the mammalian antiglycan immune response and define glycan epitopes for novel synthetic glycoconjugate vaccines against , , , and other bacteria. The chemical tools described here help us gain fundamental insights into how the human system recognizes carbohydrates and drive the discovery of carbohydrate vaccines.
ISSN:0009-2665
1520-6890
1520-6890
DOI:10.1021/acs.chemrev.0c01210