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Structure-Guided Design of a Group B Streptococcus Type III Synthetic Glycan-Conjugate Vaccine.
- Source :
-
Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2020 Jun 02; Vol. 26 (31), pp. 7018-7025. Date of Electronic Publication: 2020 Apr 01. - Publication Year :
- 2020
-
Abstract
- Identification of glycan functional epitopes is of paramount importance for rational design of glycoconjugate vaccines. We recently mapped the structural epitope of the capsular polysaccharide from type III Group B Streptococcus (GBSIII), a major cause of invasive disease in newborns, by using a dimer fragment (composed of two pentasaccharide repeating units) obtained by depolymerization complexed with a protective mAb. Although reported data had suggested a highly complex epitope contained in a helical structure composed of more than four repeating units, we showed that such dimer conjugated to a carrier protein with a proper glycosylation degree elicited functional antibodies comparably to the full-length conjugated polysaccharide. Here, starting from the X-ray crystallographic structure of the polysaccharide fragment-mAb complex, we synthesized a hexasaccharide comprising exclusively the relevant positions involved in binding. Combining competitive surface plasmon resonance and saturation transfer difference NMR spectroscopy as well as in-silico modeling, we demonstrated that this synthetic glycan was recognized by the mAb similarly to the dimer. The hexasaccharide conjugated to CRM <subscript>197</subscript> , a mutant of diphtheria toxin, elicited a robust functional immune response that was not inferior to the polysaccharide conjugate, indicating that it may suffice as a vaccine antigen. This is the first evidence of an X-ray crystallography-guided design of a synthetic carbohydrate-based conjugate vaccine.<br /> (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
Details
- Language :
- English
- ISSN :
- 1521-3765
- Volume :
- 26
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Publication Type :
- Academic Journal
- Accession number :
- 32058627
- Full Text :
- https://doi.org/10.1002/chem.202000284