Synthesis of oligosaccharide libraries from GBS capsular polysaccharides for structure-based selection of vaccine candidates
Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein.
- Del Bino, L.
- 28 October 2020
- Thesis in Leiden Repository
Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein. In the absence of structural information, long poly- or oligosaccharides extracted from bacteria are employed to cover all relevant glyco epitopes and elicit an effective immune response. The comprehension of the structural basis for the immune recognition of carbohydrate antigens and the elucidation of minimal epitopes is key to understand their mechanism of action and support the rational design of modern glycoconjugate vaccines.Group B streptococcus (GBS) is a Gram-positive bacterium, cause of infections in pregnant women and newborns, whose capsular polysaccharide (CPS) is a major virulence factor.A small library of GBS glycans from serotypes Ia, Ib and III CPSs was synthesized. These oligosaccharides were used to model the conformational preferences of the corresponding CPS and to characterize the interactions to protective anti PS monoclonal antibodies. Conjugation to carrier proteins of the most promising fragments and evaluation in vivo of the obtained glycoconjugates showed that a hexasaccharide corresponding to the minimal structural epitope of GBS III was able to elicit anti PSIII functional IgGs. Overall, the findings described in this Thesis open the path to the design of GBS vaccines based on synthetic oligosaccharides.