Effect of the nonreducing end of Shigella dysenteriae type 1 O-specific oligosaccharides on their immunogenicity as conjugates in mice.
Identifieur interne : 002B63 ( Main/Exploration ); précédent : 002B62; suivant : 002B64Effect of the nonreducing end of Shigella dysenteriae type 1 O-specific oligosaccharides on their immunogenicity as conjugates in mice.
Auteurs : Vince Pozsgay [États-Unis] ; Joanna Kubler-Kielb ; Rachel Schneerson ; John B. RobbinsSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2007.
Descripteurs français
- KwdFr :
- MESH :
- biosynthèse : Antigènes O.
- génétique : Shigella dysenteriae.
- immunologie : Anticorps, Antigènes O, Shigella dysenteriae.
- sang : Anticorps.
- Animaux, Antigènes O, Bovins, Immunogénétique, Souris, Structure moléculaire.
English descriptors
- KwdEn :
- MESH :
- chemical , biosynthesis : O Antigens.
- chemical , blood : Antibodies.
- chemical , chemistry : O Antigens.
- chemical , classification : O Antigens.
- chemical , immunology : Antibodies, O Antigens.
- genetics : Shigella dysenteriae.
- immunology : Shigella dysenteriae.
- Animals, Cattle, Immunogenetics, Mice, Molecular Structure.
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.
DOI: 10.1073/pnas.0706969104
PubMed: 17726093
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">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.</div>
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