Synthesis and immunological activity of an oligosaccharide-conjugate as a vaccine candidate against Group A Streptococcus

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 22; pp. 6038 - 6042
• Main Authors: Auzanneau, France-Isabelle, Borrelli, Silvia, Pinto, B. Mario
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-11-2013
• Subjects: Animals; Antibody Formation; Carbohydrate Sequence; Cell-wall polysaccharide; Female; Glycoconjugate; Group A Streptococcus; Immunoconjugates - chemistry; Immunoconjugates - immunology; Immunoconjugates - pharmacology; Immunogenicity; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Polysaccharides, Bacterial - chemical synthesis; Polysaccharides, Bacterial - immunology; Polysaccharides, Bacterial - pharmacology; Streptococcal Infections - immunology; Streptococcal Infections - prevention & control; Streptococcal Vaccines - chemical synthesis; Streptococcal Vaccines - immunology; Streptococcal Vaccines - pharmacology; Streptococcus; Tetanus Toxoid - chemical synthesis; Tetanus Toxoid - immunology; Vaccine candidate; Group A Streptococcus; Vaccine candidate; Glycoconjugate; Immunogenicity; Cell-wall polysaccharide
• DOI: 10.1016/j.bmcl.2013.09.042
• EISSN: 1464-3405
• ISSN: 0960-894X

The synthesis and immunogenicity of a tetanus toxoid (TT)-conjugate of the hexasaccharide portion of the cell-wall polysaccharide (CWPS) of the Group A Streptococcus (GAS) is described. The synthesis relies on the reaction of an allyl glycoside of the hexasaccharide with cysteamine, followed by the reaction of the resultant amine with diethyl squarate to give the monoethyl squarate adduct. Subsequent reaction with the lysine ε-amino groups on TT gives the glycoconjugate containing 30 hexasaccharide haptens per TT molecule. The immunogenicity in mice is similar to that obtained with a native CWPS–TT conjugate, validating the glycoconjugate as a vaccine candidate against GAS infections.