Expression of Shigella dysenteriae serotype 1 O-antigenic polysaccharide by Shigella flexneri aroD vaccine candidates and different S. flexneri serotypes.
The potential utility of Shigella flexneri aroD vaccine candidates for the development of bi- or multivalent vaccines has been explored by the introduction of the genetic determinants rfp and rfb for heterologous O antigen polysaccharide from Shigella dysenteriae serotype 1. The serotype Y vaccine strain SFL124 expressed the heterologous antigen qualitatively and quantitatively well, qualitatively in the sense of the O antigen polysaccharide being correctly linked to the S. flexneri lipopolysaccharide R3 core oligosaccharide and quantitatively in the sense that typical yields were obtained, with ratios of homologous to heterologous O antigen being 4:1 for one construct and 1:1 for another. Moreover, both polysaccharide chains were shown to be linked to position O-4 of the subterminal D-glucose residue of the R3 core. In contrast to the hybrid serotype Y SFL124 derivatives, analogous derivatives of serotype 2a vaccine strain SFL1070 did not elaborate a complete heterologous O antigen. Such derivatives, and analogous derivatives of rough, O antigen-negative mutants of SFL1070, formed instead a hybrid lipopolysaccharide molecule consisting of the S. flexneri lipid A R3 core with a single repeat unit of the S. dysenteriae type 1 O antigen. Introduction of the determinants for the S. dysenteriae type 1 O antigen into a second serotype 2a strain and into strains representing other serotypes of S. flexneri, revealed the following for the expression of the heterologous O antigen: serotypes 1a, 1b, 2a, and 5a did not produce the heterologous O antigen, whereas serotypes 2b, 3a, 3b, 4a, 4b, 5b, and X did.
Fält
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Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institute, Huddinge, Sweden.
Schweda
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Klee
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Singh
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Floderus
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Timmis
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KN
Lindberg
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D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005798:Genes, Bacterial; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D019081:O Antigens; D009844:Oligosaccharides / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis* / Q000737:chemistry; D012703:Serotyping; D012762:Shigella dysenteriae / Q000235:genetics / Q000276:immunology*; D012763:Shigella flexneri / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D009687:Nuclear Proteins; D019081:O Antigens; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C079397:rfb protein, Bacteria