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Relative stability of meningococcal serogroup A and X polysaccharides
F Berti1, M R Romano, F Micoli
1Novartis Vaccines, Via Fiorentina 1, I-53100 Siena, Italy. francesco.berti@novartis.com
Abstract:
Prior to the introduction of the MenAfriVac™ serogroup A glycoconjugate vaccine in September 2010, serogroup A was the major epidemic disease-causing meningococcal serogroup in the African meningitis belt. However, recently serogroup X meningococcal (MenX) disease has received increased attention because of outbreaks recorded in this region, with increased endemic levels of MenX disease over the past 2 years. Whereas polysaccharide-protein conjugate vaccines against meningococcal serogroups A, C, W and Y (MenA, MenC, MenW, MenY) are on the market, a vaccine able to protect against MenX has never been achieved. The structure of serogroup A, C, W and Y meningococcal polysaccharides has been already fully elucidated by NMR. MenX capsular polysaccharide (MenX CPS) structure is also documented but fewer characterization data have been published. We have applied here (1)H NMR, (31)P NMR and HPLC to evaluate the stability of MenX CPS in aqueous solution as compared to MenA capsular polysaccharide (MenA CPS). The stability study demonstrated that MenA CPS is more susceptible to hydrolytic degradation than MenX CPS. The different stereochemistry of the N-acetyl group at position C(2) of mannosamine (MenA CPS) and glucosamine (MenX CPS) respectively might play a fundamental role in this susceptibility to polysaccharide chain degradation. The satisfactory stability of MenX CPS predicts the possibility that a stable fully-liquid MenX polysaccharide or glycoconjugate vaccine could be developed.
Insights
Meningococcal serogroup X (MenX) capsular polysaccharide (CPS) is more stable than serogroup A (MenA) CPS. This finding suggests a stable, fully-liquid MenX vaccine is possible, addressing a critical unmet need.
Area of Science:
- Vaccinology
- Microbiology
- Biochemistry
Background:
- Serogroup A meningococcal (MenA) vaccines are available, but serogroup X (MenX) disease is an emerging threat in the African meningitis belt.
- Currently, no licensed vaccine protects against MenX disease, creating a significant public health gap.
- Previous research has characterized the structures of MenA, MenC, MenW, and MenY polysaccharides, but MenX polysaccharide characterization is less complete.
Purpose of the Study:
- To compare the stability of MenX capsular polysaccharide (CPS) with MenA CPS in aqueous solution.
- To investigate the structural basis for any observed differences in stability.
- To assess the potential for developing a stable MenX vaccine.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy ((1)H and (31)P) was used to analyze polysaccharide structure and stability.
- High-Performance Liquid Chromatography (HPLC) was employed to evaluate degradation.
- Stability studies were conducted in aqueous solutions.
Main Results:
- MenA CPS demonstrated greater susceptibility to hydrolytic degradation compared to MenX CPS.
- The stereochemistry of the N-acetyl group differs between MenA (mannosamine) and MenX (glucosamine) CPS, potentially influencing stability.
- MenX CPS exhibited satisfactory stability under the tested conditions.
Conclusions:
- The superior stability of MenX CPS compared to MenA CPS is a promising finding for vaccine development.
- A stable, fully-liquid MenX polysaccharide or glycoconjugate vaccine may be feasible.
- Further research into MenX CPS stability could lead to effective MenX disease prevention strategies.
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