Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates.

Abstract

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.

• Authors: John B Robbins, Joanna Kubler-Kielb, Evguenii Vinogradov, Christopher Mocca, Vince Pozsgay, Joseph Shiloach, Rachel Schneerson
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 19 Pg. 7974-8 (May 12 2009) ISSN: 1091-6490 [Electronic] United States
• PMID: 19346477 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies
• Bacterial Vaccines
• Glycoconjugates
• Immunoglobulin G
• Lipopolysaccharides
• O Antigens

Topics

• Animals
• Antibodies (chemistry)
• Bacterial Vaccines (chemical synthesis, chemistry)
• Dysentery, Bacillary (immunology, prevention & control)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoconjugates (chemistry)
• Hydrogen-Ion Concentration
• Immunoglobulin G (chemistry)
• Lipopolysaccharides (chemistry)
• Magnetic Resonance Spectroscopy
• Mice
• O Antigens (chemistry)
• Shigella sonnei (immunology)
• Spectrometry, Mass, Electrospray Ionization