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A Synthetic Glycan Array Containing Cryptococcus Neoformans Glucuronoxylomannan Capsular Polysaccharide Fragments Allows the Mapping of Protective Epitopes

preprint
submitted on 28.02.2020 and posted on 02.03.2020 by Lorenzo Guazzelli, Rebecca Ulc, Anthony Bowen, Conor Crawford, Orla McCabe, Anne J. Jedlicka, Maggie P. Wear, Arturo Casadevall, Stefan Oscarson
A block synthetic strategy to Cryptococcus neoformans glucuronoxylomannan (GXM) capsular polysaccharide part structures has been developed based on di-, tri-, tetra-, penta- and hexasaccharide thioglycoside building blocks. The approach permitted the synthesis of a library of spacer-containing serotype A and D related GXM oligosaccharide structures, ranging from di- to octadecasaccharides. Ten deprotected GXM compounds (mono- to decasaccharide) were printed onto microarray plates and screened with seventeen mouse monoclonal antibodies (mAbs) to GXM. For the first time a GXM oligosaccharide structure (a serotype A decasaccharide), capable of being recognized by neutralizing forms of these GXMspecific mAbs, has been identified, offering insight into the binding epitopes of a range of protective monoclonal antibodies and furthering our efforts to develop semi-synthetic conjugate vaccine candidates against C. neoformans.

History

Email Address of Submitting Author

stefan.oscarson@ucd.ie

Institution

University College Dublin

Country

Ireland

ORCID For Submitting Author

0000-0002-8273-4918

Declaration of Conflict of Interest

None

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