Target intelligence / Profile preview

Shigella flexneri 2a lipopolysaccharide (SF2a LPS)

Target
SF2a LPS
Molecular classification
Bacterial lipopolysaccharide, Surface antigen, Endotoxin, Glycolipid
01

Overview

Shigella flexneri 2a lipopolysaccharide (LPS) is a complex glycolipid anchored in the outer membrane of the Gram-negative bacterium Shigella flexneri 2a, a leading cause of moderate-to-severe bacillary dysentery in low- and middle-income countries. The molecule is composed of three distinct domains: the Lipid A moiety, which acts as a potent endotoxin; the core oligosaccharide; and the O-antigen (O-polysaccharide), which consists of repeating pentasaccharide units that define the 2a serotype. The O-antigen is highly immunogenic and serves as the primary target for the development of protective immunity and vaccines, as antibodies against it are strongly correlated with protection against reinfection. (Source: PMC4832549, PubMed: 30584488). In clinical development, SF2a LPS is used as the antigenic component in several glycoconjugate vaccine candidates, where the O-polysaccharide is chemically linked to carrier proteins like Tetanus Toxoid or CRM197 to enhance T-cell dependent immune responses. Beyond vaccines, the Lipid A portion of the LPS is the target for cationic antimicrobial peptides and polymyxins, which disrupt the bacterial membrane. Because Shigella flexneri 2a is one of the most prevalent serotypes globally, targeting its LPS remains a cornerstone of strategies to reduce the global burden of diarrheal disease. (Source: Lancet Infectious Diseases 2019, PubMed: 28243141).

Other names
Shigella flexneri 2a O-antigenS. flexneri 2a endotoxinShigella flexneri serotype 2a O-specific polysaccharideO-antigenic polysaccharide of Shigella flexneri 2a
02

Mechanism of action

Vaccines targeting this molecule induce the production of O-antigen-specific serum IgG and mucosal IgA antibodies that provide protection by facilitating bacterial opsonophagocytosis, complement-mediated killing, or preventing bacterial attachment to the intestinal epithelium. Antibiotics like Polymyxins bind to the Lipid A component to disrupt the bacterial outer membrane.

03

Biological functions

Bacterial cell wall structural integrityVirulence factorProtection from host immune defenseEndotoxin-mediated inflammatory responseSerotype specificity
04

Disease associations

ShigellosisBacillary dysenteryInfectionInflammation
05

Safety considerations

Endotoxicity associated with Lipid A (TLR4 activation)Reactogenicity in conjugate vaccinesSerotype replacement (escape mutants)Chemical stability of the O-antigen during vaccine formulation
06

Interacting drugs

Flexyn2a

4 more in the full profile.

07

Biomarkers

Serum anti-LPS IgG titersFecal anti-LPS IgA levelsSerum bactericidal activity (SBA) against S. flexneri 2aLPS-specific Antibody-Secreting Cells (ASCs)

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