Rhamno-oligosaccharide-based glycoconjugates as promising vaccine candidates against Group A Streptococcus

Group A Streptococcus (GAS) infections pose a serious threat to human health, with no commercial vaccines currently available. The group A carbohydrate (GAC) polyrhamnose backbone has garnered significant attention as a potential target antigen for the development of safe and effective anti-GAS vaccines. In this study, we synthesized structurally well-defined tri-, tetra-, penta-, and hexasaccharide fragments and conjugated them with an inactive mutant of Group A streptococcal C5a peptidase (ScpA193) to create novel bivalent glycoconjugate vaccine candidates. Immunological studies revealed that these semisynthetic glycoconjugates induced robust and comparable T-cell-dependent immune responses, which effectively recognize and bind to inactivated GAS (InGAS) cells in vitro, with the glycoconjugate of GA-II-2 showing particularly favorable results. Further in vivo evaluations demonstrated that glycoconjugate GA-II-2 elicited long-term immunological memory and exhibited low systematic toxicity. Additionally, glycoconjugate GA-II-2 demonstrated good recognition when tested against sera from anti-streptolysin O (ASO)-positive patients. In conclusion, the glycoconjugate GA-II-2 was identified as a highly promising GAS vaccine candidate that warrants further investigation and development.