Dissertation

Synthesis, structure and epitope mapping of well-defined Staphylococcus aureus capsular polysaccharides

This dissertation presents the synthesis and evaluation of antibody recognition for various capsular polysaccharide (CP) fragments of Staphylococcus aureus (S. aureus).

Author: K.E.R. Østerlid
Date: 22 May 2025
Links: Thesis in Leiden Repository

Previous glycoconjugate vaccine candidates to combat S. aureus infections, that made use of isolated CP5 and CP8, have all failed in late-stage clinical trials, prompting the focus on well-defined synthetic materials. The synthesized CP fragments that have been studied include type 8, type 5, and type 1. To facilitate conjugation, all these saccharides were equipped with an amino-functionalized linker. All these CP-fragments were built up from rare monosaccharides, that were synthesized in effective multi-step routes from commercially available materials. A method for constructing longer saccharides was developed, utilizing a [3+3n] glycosylation approach that reduced the number of glycosylation steps. The synthetic oligosaccharides of CP5 and CP8 were shown to induce an antibody response and the recognition of the longer synthetic fragments were consistent with that of the natural polysaccharide, providing a model for further understanding the immunology of glycoconjugate vaccines against S. aureus.