Exploring the Group B Streptococcus capsular polysaccharides: the structural diversity provides the basis for development of NMR-based identity assays

Abstract

Carbohydrate-based vaccines constitute a potent tool for prevention of life-threatening bacterial infectious diseases like meningitis and pneumonia. Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis, particularly in infants born from mothers carrying the bacteria, and no vaccine is currently available. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been found to be an extremely robust tool for tracking the industrial process manufacturing of carbohydrate-based vaccines. Here we review the differences in the repeating unit structures of GBS capsular polysaccharide (CPS) type (Ia, Ib, II-VIII) yielding unique NMR proton profiles. All the profiles provided opportunities for selecting well resolved signals, in particular in the anomeric, the methylene protons at position C3 of N-acetyl-neuraminic acid (NeupNAc) and the N-Acetyl regions, which could be employed to develop an identity assay for monovalent vaccine bulks. Finally we reported a preliminary proof of concept of identity testing on a GBS CPS type Ia, Ib, III trivalent vaccine as blended bulks, based on the selection of one specific signal for each type in the anomeric region.

Keywords: Bacterial diseases; Capsular polysaccharide; Group B Streptococcus; Nuclear Magnetic Resonance spectroscopy; Vaccine.