Abstract:
Pseudomonas aeruginosa is a multidrugresistant opportunistic pathogen causing severe nosocomial infections. Its surface lipopolysaccharide and exopolysaccharides are key targets for glycoconjugate vaccine development. Chemical synthesis provides structurally defined, homogeneous and contaminant-free oligosaccharide antigens, enabling precise epitope identification and rational vaccine design. This review systematically summarizes recent advances in the chemical synthesis and immunological evaluation of P. aeruginosaassociated glycans. Synthetic strategies include linear assembly, convergent glycosylation, onepot multicomponent synthesis and postglycosylation oxidation. Solutions to challenges such as stereoselective construction of 1, 2-cis-glycosidic linkages, introduction of rare deoxy amino sugars, orthogonal protection and latestage nonsaccharide modifications are highlighted. Successful syntheses of Oantigen repeating units from serotypes O1, O3, O4, O5, O7, O10, O11, O17, O19, ATCC 27577, NCTC 8505, core oligosaccharides, and exopolysaccharide fragments (alginate, Psl, Pel) are described. On the immunological front, epitope recognition using monoclonal antibodies and patient sera, as well as glycan microarray identification of key antigenic determinants, are discussed. Several CRM₁₉₇ conjugates induced strong Tcelldependent IgG responses and provided broad protection in animal models. Current challenges (low synthetic efficiency, insufficient stereocontrol, unsystematic immunological evaluation) and future directions are analyzed. This review aims to guide the development of synthetic glycoconjugate vaccines against P. aeruginosa.