Dissertation

Targeting bacterial pathogens with next-generation glycoconjugate vaccines

This thesis investigates innovative and classical strategies in glycoconjugate vaccine development to address the growing threat of multidrug-resistant bacterial infections.

Author

C.E.J. Sorieul

Date

19 February 2026

Links

Thesis in Leiden Repository

Chapter 1 reviews the immunological mechanisms of glycoconjugate vaccines and recent advances in vaccine platforms targeting the ESKAPE pathogens. Chapter 2 presents a proof-of-concept multivalent glycoconjugate vaccine targeting Staphylococcus aureus and Pseudomonas aeruginosa through a multimeric fusion protein of the cytotoxins Hla and PcrV, which function as both carrier proteins and antigens. A site-selective conjugation strategy enabled the attachment of S. aureus serotype 8 capsular polysaccharides while preserving antigen integrity. Chapter 3 evaluates the immunogenicity of a rhamnose-rich polysaccharide from Streptococcus suis using a revisited, classical reducing-end conjugation approach. Chapter 4 examines the interaction of a synthetic zwitterionic oligosaccharide with major histocompatibility complex class II molecules, probing the unique T cell-activating properties of zwitterionic glycans. Chapter 5 summarizes the findings and experimental challenges of the thesis, as well as outlines future directions for glycoconjugate vaccine design.

• carbohydrate-based vaccines
• glycoconjugate vaccines
• glycoimmunology
• hla
• site-selective conjugation
• vaccines
• zwitterionic polysaccharides