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Pseudomonas aeruginosa Exotoxin A (EPA) is a 66 kDa bacterial protein that serves as a potent ADP-ribosyltransferase, inhibiting host cell protein synthesis by modifying elongation factor 2 (UniProt P11439). In its detoxified recombinant form (rEPA), it is widely utilized as a carrier protein in conjugate vaccines, most notably for the Shigella O-polysaccharide (O-SP) (Cohen et al., 1997). Because bacterial polysaccharides are T-cell independent antigens that fail to induce robust memory or protection in young children, they are covalently linked to EPA to recruit T-helper cell involvement. This conjugation converts the O-SP into a T-cell dependent antigen, promoting the development of high-affinity IgG antibodies and long-lived memory B-cells (Hatz et al., 2015). EPA is particularly favored in modern bioconjugation platforms, such as those used for the Flexyn2a vaccine candidate, due to its ability to be efficiently glycosylated in engineered E. coli systems (Wacker et al., 2014). Its use helps overcome the limitations of traditional carriers like tetanus or diphtheria toxoids, which can sometimes suffer from reduced efficacy due to carrier-induced epitopic suppression (Riddle et al., 2016).
Acts as a T-cell dependent carrier protein that provides peptide epitopes for MHC II presentation to T-helper cells, thereby stimulating B-cell isotype switching and memory formation against the conjugated Shigella O-polysaccharide (Cohen et al., 1997; Wacker et al., 2014).
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