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  • Title: Towards a vaccine candidate against Shigella dysenteriae 1: expression of the Shiga toxin B-subunit in an attenuated Shigella flexneri aroD carrier strain.
    Author: Tzschaschel BD, Klee SR, de Lorenzo V, Timmis KN, Guzmán CA.
    Journal: Microb Pathog; 1996 Oct; 21(4):277-88. PubMed ID: 8905616.
    Abstract:
    Shiga toxin is considered to be one of the main causes of severe side effects, such as the hemolytic uremic syndrome, of shigellosis. The genetic determinants for a fusion of its B-subunit (StxB), which mediates toxin binding to target cells, with the COOH-terminus of Escherichia coli hemolysin A (Stx'-'HlyA) has been combined with the determinants of the accessory translocator proteins HlyB and HlyD in a Notl cassette. This cassette has been integrated via a mini-transposon into a recombinant vaccine strain that expresses Shigella flexneri Y and Shigella dysenteriae 1 O-antigen lipopolysaccharides. Characterisation of the resulting strains showed that they maintain all the vaccine-relevant biological properties of the carrier and export efficiently the StxB'-'Hly A fusion peptide into the culture medium. Polyclonal antibodies raised against the StxB'-'HlyA fusion exhibited neutralizing activity in the HeLa cytotoxicity assay. The newly developed strains thus represent promising bivalent vaccine candidates against severe shigellosis caused by S. dysenteriae 1 and S. flexneri Y.
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