Target intelligence / Profile preview

Adaptive immune system (Shigella flexneri 2a O-polysaccharide recognition)

Molecular classification
Other, Immune System
01

Overview

The adaptive immune system's recognition of the Shigella flexneri 2a O-polysaccharide–EPA conjugate is the fundamental mechanism for inducing protective immunity against shigellosis (Riddle et al., 2016, The Lancet Infectious Diseases). Shigella flexneri is a Gram-negative bacterium and a leading cause of bacillary dysentery worldwide, especially in pediatric populations in developing regions (Cohen et al., 2014, Expert Review of Vaccines). The O-polysaccharide (O-antigen) is a key virulence factor and a primary target for protective antibodies, but as a pure polysaccharide, it is poorly immunogenic and does not induce memory. By conjugating the O-polysaccharide to a carrier protein like Pseudomonas aeruginosa Exoprotein A (EPA), the antigen is transformed into a T-cell dependent form (van der Put et al., 2023, Vaccines). This allows the adaptive immune system to engage T-helper cells, leading to robust B-cell activation, isotype switching to IgG, and the formation of memory B cells. Clinical candidates like Flexyn2a utilize this approach to elicit high titers of serum anti-LPS IgG, which are used as primary markers of vaccine efficacy (Riddle et al., 2016). The interaction between the conjugate and the immune system aims to prevent the invasion of the colonic epithelium by Shigella through antibody-mediated neutralization or bactericidal activity. Therapeutic development in this area focuses on overcoming the serotype-specific nature of the O-antigen to provide broad protection against various Shigella species.

Other names
Shigella flexneri 2a O-antigen immunityAnti-LPS immune responseFlexyn2a-induced immunityAdaptive immunity to Shigella bioconjugate
02

Mechanism of action

Induction of a T-cell dependent immune response against the Shigella flexneri 2a O-polysaccharide, resulting in the production of specific serum IgG antibodies and long-term immunological memory.

03

Biological functions

Immune responseAntibody productionImmunological memoryT-cell dependent B-cell activation
04

Disease associations

InfectionShigellosisDiarrheal disease
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Safety considerations

Injection site painErythemaFeverHeadacheMalaise
06

Interacting drugs

Flexyn2a

1 more in the full profile.

07

Biomarkers

Serum anti-Shigella flexneri 2a LPS IgG titersSerum bactericidal activity (SBA)Antigen-specific memory B cellsFecal IgA

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