Synthesis and immunological studies of group A Streptococcus cell-wall oligosaccharide–streptococcal C5a peptidase conjugates as bivalent vaccines

Abstract

Group A Streptococcus (GAS) cell-wall polysaccharides and streptococcal C5a peptidase (ScpA) are identified as potential target antigens for the development of anti-GAS vaccines. Structurally well-defined mono-, di-, and trimers of the trisaccharide repeating unit of the major and conserved cell-wall polysaccharide of various GAS serotypes were synthesized by a convergent and efficient strategy. These synthetic oligosaccharides, which had a free amino group at the reducing end, were conjugated with a novel ScpA mutant ScpA193 protein through the bifunctional glutaryl linker. The resultant neoglycoproteins were evaluated as conjugate vaccines and compared with other glycoconjugates using the common carrier proteins diphtheria toxin mutant CRM197 and tetanus toxoid (TT). Immunological studies using mice revealed that the ScpA193 conjugates could stimulate not only robust GAS oligosaccharide-specific antibody responses that were comparable to the immunological activities of CRM197 and TT conjugates but also robust ScpA193-specific antibodies, making the ScpA193–oligosaccharide conjugates promising bivalent anti-GAS vaccine candidates.