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The Shigella flexneri 2a O-polysaccharide (O-PS) is the primary surface antigen and a critical virulence factor of the Gram-negative bacterium Shigella flexneri serotype 2a, which is a leading cause of bacillary dysentery (shigellosis) worldwide [12, 14]. It constitutes the distal, repeating carbohydrate portion of the lipopolysaccharide (LPS) and determines the serotype specificity of the organism through its unique arrangement of rhamnose and N-acetylglucosamine residues, often modified by glucose and O-acetyl groups [11, 15]. Biologically, the O-PS protects the bacterium from host environmental stresses and immune mechanisms, such as complement-mediated killing, while facilitating intestinal colonization and invasion [14, 16]. Because natural infection induces protective, serotype-specific antibodies against the O-PS, it has become a central target for vaccine development [5, 8]. Current therapeutic strategies focus on glycoconjugate vaccines, where the O-PS is covalently linked to carrier proteins like Pseudomonas aeruginosa exotoxin A (EPA) or tetanus toxoid to enhance immunogenicity, particularly in infants [3, 13]. Clinical candidates such as Flexyn2a have demonstrated the ability to elicit functional, bactericidal IgG and IgA antibodies that correlate with reduced disease severity in human challenge models [4, 17].
Induction of protective humoral immunity through the production of O-antigen-specific IgG and IgA antibodies, which mediate serum bactericidal activity (SBA) and prevent bacterial colonization and invasion of the intestinal epithelium [3, 4, 17].
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