title: Effect of the nonreducing end of Shigella dysenteriae type 1 O-specific oligosaccharides on their immunogenicity as conjugates in mice.
abstract: Endemic and epidemic shigellosis, an acute invasive disease of the lower intestines, afflicts millions of people worldwide with an estimated one million fatalities per annum at a low infectious dose. Our approach to vaccine development against Shigella is based on the hypothesis that serum IgG antibodies to the O-specific polysaccharide (O-SP) domains of the LPS of these organisms confer protection to infection. The synthetic oligosaccharides corresponding to the tetrasaccharide repeating unit of the O-SP of Shigella dysenteriae type 1 covalently linked to human serum albumin elicited O-SP-specific IgG in mice. The antibody levels were a function of both the saccharide chain length and their loading on the protein. These synthetic saccharide conjugates elicited significantly higher levels of IgG anti O-SP than conjugates prepared with the O-SP from the bacteria. Here, we evaluated the influence of the nonreducing terminal monosaccharide on the serum antibody response. To this end, we prepared synthetic oligosaccharides comprising hexa- to tridecasaccharide fragments of the native O-SP, having one of the four monosaccharide residues that constitute the repeating unit at their termini and bound them to BSA by a single-point attachment. The conjugates contained an average of 19 saccharide chains per BSA. The synthetic oligosaccharides inhibited the binding of serum raised against whole bacteria to its LPS to a similar extent but lower than the native O-SP. The highest anti-LPS levels were elicited by conjugates having N-acetylglucosamine (10-mer) or galactose residues (7- and 11-mers) at their nonreducing termini.
authors.affiliation: Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2423, USA. pozsgayv@mail.nih.gov
authors.forename: Vince
authors.initials: V
authors.lastname: Pozsgay
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubler-Kielb
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D002417:Cattle; D007125:Immunogenetics; D051379:Mice; D015394:Molecular Structure; D019081:O Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000145:classification* / Q000276:immunology*; D012762:Shigella dysenteriae / Q000235:genetics* / Q000276:immunology*
chemical_list: D000906:Antibodies; D019081:O Antigens