Advancing modern glycoconjugate vaccines: From synthetic glycans to novel conjugation approaches and carrier systems

Glycoconjugate vaccines have significantly impacted the prevention of numerous bacterial infectious diseases, yet challenges remain in developing new vaccine candidates against emerging and drug-resistant pathogens. This review highlights key advancements in bacterial glycoconjugate vaccine research over the last two years, focusing on three critical areas: the use of chemically or chemoenzymatically synthesized glycans to elucidate structure-immunogenicity relationships and to produce semisynthetic glycoconjugates, innovations in conjugation methods (including chemical site-selective approaches and glycoengineering), and the development of novel protein and nanocarriers. Recent studies demonstrate significant progress in structure guided vaccine design through synthetic glycan epitopes, achieving molecularly homogeneous conjugates with site-selective conjugation and bioconjugation, and enhancing immunogenicity with novel nanocarriers. This review synthesizes these developments over the last two years and identifies future directions for rational vaccine design.