Group B Streptococcus chimeric capsular polysaccharides as novel multivalent vaccine candidates

Area of Science:

• Microbiology
• Immunology
• Vaccine Development

Background:

• Group B Streptococcus (GBS) capsular polysaccharide is a critical virulence factor and vaccine target.
• Ten GBS serotypes exist, each with unique antigenic properties, necessitating multi-component vaccines for broad protection.
• GBS polysaccharide synthesis involves a conserved polymerase-dependent pathway encoded by a polycistronic operon.

Purpose of the Study:

• To engineer a single GBS polysaccharide molecule combining epitopes from serotypes V and IX.
• To assess the immunogenicity and protective efficacy of chimeric glycoconjugates derived from these engineered polysaccharides.
• To establish proof of concept for a new generation of multi-valent glycoconjugate vaccines.

Main Methods:

• Exploited sequence similarity in capsule operons of GBS serotypes V and IX.
• Co-expressed specific glycosyltransferases (CpsM, O, I) to generate hybrid polysaccharides.
• Produced chimeric glycoconjugates and evaluated physicochemical and immunochemical properties.
• Assessed vaccine efficacy in a mouse model challenged with GBS serotypes V and IX.

Main Results:

• Successfully produced a high molecular weight chimeric polysaccharide with combined antigenic specificities of GBS types V and IX.
• Optimized glycosyltransferase gene copy number to modulate the ratio of type-specific epitopes.
• Vaccination with chimeric glycoconjugates significantly reduced disease incidence in mice challenged with either serotype V or IX.

Conclusions:

• Demonstrated the feasibility of creating single-molecule, multi-serotype GBS polysaccharides.
• Validated the protective potential of chimeric glycoconjugates against multiple GBS serotypes.
• This approach offers a promising strategy for developing broadly protective GBS vaccines.