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Published on: November 2, 2021
Exploring the Group B Streptococcus capsular polysaccharides: the structural diversity provides the basis for
Vittoria Pinto1, Francesco Berti1
1Novartis Vaccines, Via Fiorentina 1, I-53100 Siena, Italy.
Insights
Nuclear Magnetic Resonance (NMR) spectroscopy can identify Group B Streptococcus (GBS) vaccine components. This method tracks manufacturing and can confirm vaccine identity for GBS capsular polysaccharide (CPS) types.
Area of Science:
- Vaccinology
- Analytical Chemistry
- Microbiology
Background:
- Carbohydrate-based vaccines are crucial for preventing bacterial infections like meningitis and pneumonia.
- Group B Streptococcus (GBS) causes severe neonatal infections, yet no vaccine is available.
- High-field Nuclear Magnetic Resonance (NMR) spectroscopy is effective for monitoring carbohydrate vaccine manufacturing.
Purpose of the Study:
- To review structural differences in GBS capsular polysaccharide (CPS) types (Ia, Ib, II-VIII).
- To explore the utility of unique NMR proton profiles for vaccine characterization.
- To establish an identity assay for GBS monovalent vaccine bulks.
Main Methods:
- Analysis of repeating unit structures of GBS CPS types using high-field NMR spectroscopy.
- Identification of unique NMR proton profiles for each GBS CPS type.
- Selection of well-resolved signals in anomeric, NeupNAc methylene (C3), and N-Acetyl regions.
Main Results:
- Distinct NMR proton profiles were observed for different GBS CPS types.
- Specific signals in the anomeric, C3 methylene, and N-Acetyl regions are suitable for identity assays.
- A proof of concept demonstrated identity testing of a GBS CPS type Ia, Ib, III trivalent vaccine using selected anomeric signals.
Conclusions:
- NMR spectroscopy provides unique fingerprints for GBS CPS types, enabling vaccine characterization.
- The identified NMR signals can form the basis of a robust identity assay for GBS vaccines.
- NMR-based identity testing is feasible for both monovalent and multivalent GBS vaccine formulations.
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.
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