Glycan surface antigens from Bacillus anthracis as vaccine targets: current status and future perspectives

Abstract

Over recent years great attention has been directed to the discovery of novel antigens from Bacillus anthracis, because of the potential of its spores in the development of weapons for mass destruction. Substantial effort has been directed to the identification and immunochemical evaluation of glycans that might be used for specific diagnostic detection of the spores or immune-mediated prevention of anthrax. Carbohydrate structures found on surfaces of vegetative cells and spores are herein discussed. Among them, the cell wall polysaccharide and the tetrasaccharide unit isolated from the exosporium protein BclA were proven immunogenic in an animal model after covalent linkage to carrier protein. Further investigation is needed to fully assess the potential of these promising carbohydrate antigens for vaccine development.

Keywords::

• anthrax
• carbohydrates
• cell wall polysaccharide
• exosporium
• glycoconjugates
• peptidoglycan

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Erratum

Acknowledgement

Matthew Bottomley is acknowledged for help in editing the article.

Financial & competing interests disclosure

The author is an employee of Novartis Vaccines, Italy. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Glycan structures have been identified on the surfaces of both the vegetative cell and spores.

• The secondary cell wall polysaccharide (SCWP) repeating unit and fragments thereof have been chemically synthesized and proven to be the ligands for the phage lysin G and L, two endolysins capable of lysing the bacterium.

• Antibodies against synthetic fragments of SCWP could be induced in mice following vaccination with KHL conjugates.

• A tetrasaccharide present in the more abundant glycoprotein of the exosporium, BclA, has been identified and the structure has been chemically synthesized through a variety of approaches.

• The repeating unit of SCWP and the tetrasaccharide from BclA have been chemically synthesized.

• The immunodominant residue of the tetrasaccharide structure is the nonreducing end terminal novel sugar, which is known as anthrose.

• The tetrasaccharide has been utilized for the development of specific mAbs and assays for the detection of spores.

• Protein conjugates of the tetrasaccharide and anthrose-containing fragments were proven immunogenic in an animal model.

Notes

All the sugar are in D-configuration.

Gal: Galactopyranosides; GlcNAc: 2-glucosaminopyronoside; ManNAc: Mannosaminopyranoside.

Data taken from [51].