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The O-polysaccharide (O-antigen) is the highly variable, outermost component of the lipopolysaccharide (LPS) molecule found on the surface of Salmonella enterica serovar Typhimurium. It consists of repeating oligosaccharide units—typically comprising D-galactose, L-rhamnose, and D-mannose with an abequose side branch—that define the bacterium's serological identity (O:4, [5], 12). Biologically, the O-antigen serves as a critical protective barrier, shielding the bacterium from host immune mechanisms such as complement-mediated lysis and phagocytosis, while also contributing to the structural integrity of the outer membrane. Because it is a primary surface-exposed structure, it is a major target for the host's adaptive immune system during infection. In the context of drug and vaccine development, the O-antigen is a primary target for glycoconjugate vaccines aimed at preventing salmonellosis and invasive non-typhoidal Salmonella (iNTS) disease. These vaccines typically involve chemically linking the O-polysaccharide to a carrier protein, such as CRM197 or flagellin, to convert the T-cell independent polysaccharide into a T-cell dependent antigen, thereby inducing long-lasting immunological memory. Therapeutic strategies focus on generating high titers of specific IgG antibodies that promote the opsonization and killing of the bacteria. Clinical and preclinical efforts continue to evaluate these O-antigen-based conjugates for their efficacy in high-burden regions, particularly for pediatric populations at risk of severe invasive disease.
Induction of protective opsonophagocytic and bactericidal antibodies that target the bacterial surface to facilitate pathogen clearance.
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