Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

Significance Each year, Streptococcus pneumoniae infections cause millions of deaths worldwide. The capsular polysaccharide (CPS) based glycoconjugate vaccine Prevnar13 prevents serious illness caused by 13 serotypes. S. pneumoniae serotype 5 (ST-5) is included in the vaccine; however, it suffers from production problems due to modifications or degradation during isolation and conjugation. A medicinal chemistry approach helped to understand the structural features of ST-5 CPS and design a stable semisynthetic oligosaccharide-based vaccine candidate. Oligosaccharide leads for immunological evaluations in vivo were identified employing glycan microarrays. The stable monovalent ST-5 oligosaccharide glycoconjugate vaccine candidate showed a superior immune response in rabbits when compared with the ST-5 CPS present in the multivalent vaccine Prevnar13.