Synthesis and immunogenicity evaluation of oligosaccharide epitopes for the development of a glycoconjugate vaccine against Streptococcus pneumoniae serotype 3

Streptococcus pneumoniae serotype 3 (ST3) is one of the most pathogenic bacteria that causes a variety of invasive pneumococcal diseases. The hypoimmunity of ST3 capsular polysaccharide (CPS) observed in commerical conjugate vaccines currently used prompted us to develop more effective anti-ST3 vaccines. Glycoconjugates based on ST3 CPS oligosaccharide fragments were demonstrated to induce protective IgG antibodies against ST3 and thus are recognized as promising antigen candidates for developing a novel ST3 vaccine. In this study, a series of ST3 CPS oligosaccharide derivatives with different glycan chain lengths and sequences in the structure were efficiently constructed through a one-pot preactivation glycosylation or convergent glycosylation, and the corresponding oligosaccharide-TT conjugates were subsequently prepared via the bifunctional glutaryl linker. Preliminary immunological studies in mice disclosed that all the synthesized oligosaccharide conjugates induced comparable or stronger T-cell-dependent immunity than that of the polysaccharide conjugate CPS3-TT. The antisera of these oligosaccharide conjugates also exhibited significant cross-reactivity against ST3 CPS polysaccharide, which indicated the great potential of the synthesized oligosaccharides, particularly hexasaccharide 3b, as optimal antigenic epitopes for vaccine development.