PEA is a strong virulence factor excreted by P. aeruginosa with cytotoxicity for mammalian cells to enter cells by receptor-mediated endocytosis. PEA is a class of two-component AB toxin family. This bacterial exotoxin is a protein consisting of 613 amino acids (aa) and comprises three functional domains. It also includes a highly hydrophobic leader peptide of 25 aa at its N-terminus, which is separated during secretion. The first functional domain is receptor-binding domain Ia (1-252 aa) which is made up of antiparallel β-sheets. Then comes translocation domain II (253-364 aa) which is composed of six consecutive α-helices. The last functional domain includes domain Ib (365-404 aa) and domain III (405-613 aa) with four residues (400-404 aa) that form the catalytic subunit of the toxin with ADP-ribosyltransferase activity. The catalytic enzyme activity of domain Ib and domain III ADP-ribosylates the elongation factor of the host ribosome that causes apoptotic cell death.
Fig.1 Diagrammatic drawing of the structural and functional domains of PEA. (CD BioGlyco)
CD BioGlyco provides a nontoxic mutant toxin, a recombinant PEA with no ADP-ribosylating activity. Our recombinant PEA keeps up its immunogenic effect. Therefore, this recombinant PEA is an outstanding candidate for the preparation of conjugate vaccines. This recombinant non-toxic form of PEA is useful as a carrier for Shigella O-antigens, Staphylococcus aureus type 5 and 8 capsular polysaccharides (CPS), and Salmonella typhi Vi antigen. We prepare Vi-recombinant PEA with different linkers including succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and adipic acid dihydrazide (ADH). Those conjugates we produce are safe. Moreover, they produce biologically active antibodies to both the CPS and PEA components. In addition, we make recombinant PEA to be a carrier protein that effectively supports a multi-antigenic method for the research of a conjugate vaccine. Our conjugates produce antibodies against both pathogenic P. aeruginosa O-PS and PEA, providing broad-spectrum protection from P. aeruginosa infection. These conjugates provide support for Carbohydrate-based Vaccine Development.
Fig.2 Preparation of recombinant PEA conjugate. (CD BioGlyco)
At CD BioGlyco, we often use recombinant PEA as a carrier protein due to its safety, immunogenicity, and possibility for serological cross-protection between various strains. We provide a variety of Carrier Proteins based on our Glyco™ Vaccine Development Platform. No matter which types of vaccines our clients want, we do whatever we can to meet their needs. If you are interested in our services, please feel free to contact us for more detailed information.
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