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A structurally diversified linker enhances the immune response to a small carbohydrate hapten

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Abstract

The tether employed to covalently attach β-mannan disaccharide glycoconjugates influences the specificity of rabbit antibodies that protect against Candida albicans. Two glycoconjugates containing (1 → 2)-β-mannan disaccharides linked to chicken serum albumin (CSA) either via a structurally uniform or via a stereodiversified spacer were prepared and evaluated in immunization trials in mice and rabbits. Immunization with conjugate vaccine possessing a structurally diversified linker induced higher IgG titers against Candida albicans cell wall phosphomannan than a conjugate with a structurally uniform linker. These results suggest that affinity maturation and the specific antibody response can be shifted towards recognition of the desired hapten by employing a linker with diversified configuration.

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Abbreviations

BSA:

Bovine serum albumin

CSA:

Chicken serum albumin

TMSOTf:

Trimethylsilyl trifluoromethanesulfonate

Pn14PS:

S. pneumoniae capsular polysaccharide type 14

CRM197 :

Cross Reacting Materials 197 (diphtheria toxin-related protein)

NMO:

N-Methylmorpholine N-oxide

THF:

Tetrahydrofuran

DCM:

Dichloromethane

DMSO:

Dimethylsulfoxide

DMF:

Dimethylformamide

HSQC:

Heteronuclear Single Quantum Coherence experiment

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Acknowledgements

This work was supported by a Natural Science and Engineering Council of Canada Discovery grant to DRB and by funds from an Alberta Innovates Centres program.

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Authors and Affiliations

  1. Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada

    Tomasz Lipinski, Thanh Luu, Pavel I. Kitov, Adam Szpacenko & David R. Bundle

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  1. Tomasz Lipinski
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  2. Thanh Luu
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  3. Pavel I. Kitov
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  5. David R. Bundle
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Correspondence to David R. Bundle.

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Lipinski, T., Luu, T., Kitov, P.I. et al. A structurally diversified linker enhances the immune response to a small carbohydrate hapten. Glycoconj J 28, 149–164 (2011). https://doi.org/10.1007/s10719-011-9331-8

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  • DOI: https://doi.org/10.1007/s10719-011-9331-8

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