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Detoxified Pseudomonas aeruginosa exotoxin A (EPA) is a recombinant, non-toxic variant of the potent Exotoxin A (ETA) secreted by the bacterium Pseudomonas aeruginosa [UniProt P11439]. The native toxin is a member of the mono-ADP-ribosyltransferase family, which inhibits host cell protein synthesis by modifying elongation factor 2 (EF-2), leading to cell death [PubMed: 15501764]. Detoxification is typically achieved through genetic modification, such as the deletion or substitution of the glutamic acid residue at position 553, which eliminates its enzymatic activity while preserving its ability to stimulate the immune system [Vaxcyte, 2024]. In pharmaceutical development, EPA is primarily employed as a carrier protein for conjugate vaccines targeting various bacterial pathogens, including Streptococcus pneumoniae and Shigella species [NCBI, 2023]. By chemically linking bacterial capsular polysaccharides to EPA, the vaccine can recruit T-helper cells, transforming the typically weak, T-cell independent carbohydrate response into a robust, T-cell dependent response characterized by high-affinity antibodies and immunological memory. This approach is particularly effective in inducing protective immunity in populations with immature or compromised immune systems, such as infants and the elderly [PubMed: 15501764].
Acts as a carrier protein in conjugate vaccines to provide T-cell epitopes, enabling a T-cell dependent immune response against conjugated polysaccharide antigens.
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