Shigellosis, an enteric disease, is on the World Health Organization's priority prevention list. In one study, the Shigella sonnei
O-specific polysaccharide (O-SP)-
protein conjugate showed 72% protection against disease in Israeli army recruits exposed to high rates (8-14%) of
infection. The protection was related to
vaccine-induced
IgG anti-O-SP levels. Synthetic
oligosaccharides of Shigella dysenteriae type 1, bound by their reducing ends to a
carrier protein ("sun"-type configuration), induced significantly higher antibody levels than the native O-SP bound to
protein by multiple-point attachments ("lattice"-type configuration). Attempts to synthesize the S. sonnei O-SP based
oligosaccharides were not successful. Here, we describe the isolation, characterization, and conjugation of low-molecular-mass O-SP-core (O-SPC) fragments. The O-SPC fragments were bound by their reducing ends similar to the preparation of the synthetic S. dysenteriae type 1 conjugates. The O-SPC conjugates used
oxime linkages between the terminal Kdo residues at the reducing ends of the S. sonnei saccharides and aminooxy linkers bound to BSA or a recombinant
diphtheria toxin. The coupling reaction was carried out at a neutral pH and room temperature.
IgG antibody levels induced in young outbred mice by the S. sonnei O-SPC conjugates were significantly higher then those elicited by the O-SP conjugates. Accordingly, we propose to evaluate clinically these conjugates.