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

Area of Science:

• Microbiology
• Immunology
• Organic Chemistry

Background:

• Streptococcus pneumoniae causes significant childhood disease, with 13 serotypes responsible for 90% of severe cases.
• Pneumococcal bacterial polysaccharide conjugate vaccines (PCVs) have successfully reduced disease burden.
• Serotype 31, a non-vaccine serotype, has shown increasing prevalence.

Purpose of the Study:

• To revise the structure of serotype 31 polysaccharide (s-31-ps).
• To develop a novel conjugate vaccine using s-31-ps and CRM197 protein.
• To evaluate the immunogenicity of the novel conjugate vaccine.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the s-31-ps structure.
• Reductive amination was employed to conjugate s-31-ps with CRM197 protein in N,N-dimethylformamide (DMF).
• Immune responses elicited by the DMF conjugate were compared to an aqueous conjugate.

Main Results:

• The revised structure of s-31-ps was elucidated 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.
• Conjugation in DMF was faster than in water.
• The DMF conjugate elicited immune responses comparable to the aqueous conjugate.

Conclusions:

• The revised s-31-ps structure provides a basis for vaccine development.
• A novel, efficiently prepared conjugate vaccine using s-31-ps holds promise.
• This s-31-ps conjugate vaccine could be a valuable addition to next-generation PCVs.