Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates.
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.
Robbins
John B
JB
National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. robbinsjo@mail.nih.gov
Kubler-Kielb
Joanna
J
Vinogradov
Evguenii
E
Mocca
Christopher
C
Pozsgay
Vince
V
Shiloach
Joseph
J
Schneerson
Rachel
R
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001428:Bacterial Vaccines / Q000138:chemical synthesis* / Q000737:chemistry; D004405:Dysentery, Bacillary / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D019081:O Antigens / Q000737:chemistry*; D012764:Shigella sonnei / Q000276:immunology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000906:Antibodies; D001428:Bacterial Vaccines; D006001:Glycoconjugates; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D019081:O Antigens