RESUMO
Coupling of carbohydrate antigens to protein carriers is a typical approach to enhancing the immunogenicity of carbohydrate-based vaccines. Glycoconjugates with well-defined structures are needed for studies defining the structural variables that govern antibody responses. We report a chemical strategy for preparation of an array of glycoconjugates containing saccharides of desired molecular sizes by selective depolymerization of bacterial polysaccharides and chemically controlled site-specific coupling. As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus.
Assuntos
Antígenos de Bactérias/imunologia , Glicoconjugados/imunologia , Oligossacarídeos/imunologia , Polissacarídeos Bacterianos/imunologia , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/imunologia , Cápsulas Bacterianas , Configuração de Carboidratos , Sequência de Carboidratos , Ciclobutanos , Ensaio de Imunoadsorção Enzimática , Feminino , Glicoconjugados/síntese química , Glicoconjugados/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Peso Molecular , Oligossacarídeos/isolamento & purificaçãoRESUMO
The binding of nineteen analogues of the upstream, terminal, monosaccharide residue of each of the O-polysaccharide (O-PS) of Vibrio cholerae O:1, serotype Ogawa and Inaba, with two murine monoclonal IgG antibodies both specific for the Ogawa LPS were measured using fluorescence spectroscopy. The use of the deoxy and the deoxyfluoro analogs allowed further refinement of the hydrogen-bonding pattern involved in the binding. Based on the binding characteristics observed for some of the ligands in the Inaba series, the binding of the monosaccharide that represents the upstream, terminal unit of the O-PS of V. cholerae O:1 serotype Inaba was redefined. We show for the first time that the upstream, terminal monosaccharide of the Inaba O-PS shows weak binding with these two anti-Ogawa antibodies. The results obtained allow further rationalization of the structural basis for the binding of V. cholerae O:1 antigens to their homologous antibodies.