Conjugate of structurally reassigned pneumococcal serotype 31 polysaccharide with CRM197 elicited potent immune response

Around 100 Streptococcus pneumonia (Spn) serotypes have been discovered, 90% of the severe diseases in children are caused by 13 serotypes. With the success of pneumococcal bacterial polysaccharide conjugate vaccines (PCVs), the burden of pneumococcal disease has been significantly reduced. Serotype 31 is a non-vaccine serotype and has increased in prevalence. By using Nuclear Magnetic Resonance (NMR) as the primary tool, we report the revised serotype 31 polysaccharide (s-31-ps) structure as [→3)-β-D-Galf-(5/6-OAc)-(1 → 3)-β-D-Galp-(1 → 3)-β-L-Rhap-(2-OAc)-(1 → 2)-α-L-Rhap-(1 → 4)-β-D-GlcpA-(1→]n. Furthermore, the reductive amination-conjugate of serotype 31 polysaccharide and cross reacting material (CRM197) protein was prepared in organic solvent (N,N-dimethylformamide, DMF) instead of water. The reaction is faster, and the DMF conjugate elicited comparable immune responses with the aqueous conjugate. S-31-ps conjugate vaccine has the potential of being included in the next-generation PCV vaccines.