1. Structure-based glycoconjugate vaccine design: The example of Group B Streptococcus type III capsular polysaccharide.
- Author
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Carboni, Filippo and Adamo, Roberto
- Subjects
STREPTOCOCCUS agalactiae ,MICROBIAL polysaccharides ,SURFACE plasmon resonance ,STREPTOCOCCUS thermophilus ,MAGNETIZATION transfer ,X-ray crystallography ,STREPTOCOCCUS - Abstract
• Elucidation of minimal glycan epitopes is key for vaccine design. • Application of structural glycobiology to conjugate vaccines enables identification of relevant glycan epitopes. • We solved by X-ray crystallography the highly complex epitope from GBSIII capsular polysaccharide complexed with a Fab. • Based on this information a synthetic glycan was designed and protein conjugate to induce a strong immune response. • This approach can be extended to other GBS polysaccharides as well as glycans from other pathogens. Microbial surface polysaccharides are important virulence factors and targets for vaccine development. Glycoconjugate vaccines, obtained by covalently linking carbohydrates and proteins, are well established tools for prevention of bacterial infections. Elucidation of the minimal portion involved in the interactions with functional antibodies is of utmost importance for the understanding of their mechanism of induction of protective immune responses and the design of synthetic glycan based vaccines. Typically, this is achieved by combination of different techniques, which include ELISA, glycoarray, Surface Plasmon Resonance in conjunction with approaches for mapping at atomic level the position involved in binding, such as Saturation Transfer NMR and X-ray crystallography. This review provides an overview of the structural studies performed to map glycan epitopes (glycotopes), with focus on the highly complex structure of Group B Streptococcus type III (GBSIII) capsular polysaccharide. Furthermore, it describes the rational process followed to translate the obtained information into the design of a protective glycoconjugate vaccine based on a well-defined synthetic glycan epitope. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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