Work

Modular Combinatorial DNA Assembly of Group B Streptococcus Capsular Polysaccharide Biosynthesis Pathways to Expediate the Production of Novel Glycoconjugate Vaccines

Year: 2025

Type: article

Abstract: BACKGROUND/OBJECTIVES: (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up to 99% of infections. Currently, there are no licensed vaccines against GBS. The most developed candidates are glycoconjugate vaccines, which can be highly effective but are also expensive to produce by existing approaches and unaffordable for many parts of the world. Biosynthesis of recombinant glycans and glycoconjugates in tractable strains of bacteria offers a low-cost alternative approach to current chemical conjugation methods. METHODS: . Each gene was removed from its native regulation, paired with synthetic regulatory elements and rebuilt from the bottom up to generate libraries of reconstituted pathways. These pathways were screened for glycan biosynthesis using serotype-specific antisera. RESULTS: We identified several configurations that successfully biosynthesised the GBS CPSs. Furthermore, we exploited the conserved nature of the GBS CPS biosynthesis loci and the flexibility of modular DNA assembly by constructing hybrid pathways from a minimal pool of glycosyltransferase genes. We show that transferase genes with homologous function can be used interchangeably between pathways, obviating the need to clone a complete locus for each new CPS assembly. CONCLUSIONS: , a key milestone towards the development of low-cost recombinant multivalent GBS glycoconjugate vaccines.

Source: Vaccines

DOI: 10.3390/vaccines13030279

Authors: Mark A. Harrison, Elizabeth Atkins, Alexandra Faulds-Pain, John T. Heap, Brendan W. Wren, Ian J. Passmore

Institutions: London School of Hygiene & Tropical Medicine, University of Nottingham

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258