Nuclear magnetic resonance assessment of controlled hydrolysis of the capsular polysaccharides of Streptococcus pneumoniae serotypes 19A and 19F

ABSTRACT Several glycoconjugate-based vaccines are inserted nowadays in infant vaccination schedules of most countries. In an initial stage, polysaccharides are modified under controlled conditions. The assessment of polysaccharide regions available for conjugation process after the hydrolysis is crucial to predict the conjugation results for achieving the final active pharmaceutical ingredient. Two hydrolyzed capsular polysaccharides were analyzed by a heteronuclear single-quantum correlation experiment. It was adjusted for assessing 3JP-H to check the position of phosphate mono-ester residue after the hydrolysis process. All evaluated polysaccharides have been shown to remain with the anomeric position available for subsequent conjugation. The adjusted spectroscopic experiment was shown to be effective to study the hydrolysis of phosphate di-ester linked to capsular polysaccharides.

[1]  N. Ravenscroft,et al.  Capsular polysaccharide conformations in pneumococcal serotypes 19F and 19A. , 2015, Carbohydrate research.

[2]  Maria Grazia Starita,et al.  The Regulatory Framework , 2012 .

[3]  Raine Garrido,et al.  Quantitative proton nuclear magnetic resonance evaluation and total assignment of the capsular polysaccharide Neisseria meningitidis serogroup X. , 2012, Journal of pharmaceutical and biomedical analysis.

[4]  C. Frasch,et al.  Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines , 2010, Clinical and Vaccine Immunology.

[5]  C. Frasch.  Preparation of bacterial polysaccharide-protein conjugates: analytical and manufacturing challenges. , 2009, Vaccine.

[6]  R. Kaiser,et al.  Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines by GC-MSD. , 2005, Analytical biochemistry.

[7]  Christopher Jones,et al.  NMR assays for carbohydrate-based vaccines. , 2005, Journal of pharmaceutical and biomedical analysis.

[8]  C. Lugowski,et al.  Structural determination of the capsular polysaccharide of Streptococcus pneumoniae type 18C (56). , 1983, Carbohydrate research.

[9]  H. Jennings,et al.  Structural determination of the capsular polysaccharide of Streptococcus pneumoniae type 19A (57). , 1980, Carbohydrate research.

[10]  N. Ravenscroft,et al.  Characterization of Carbohydrate Vaccines by NMR Spectroscopy. , 2015, Methods in molecular biology.

[11]  Christopher Jones.  Glycoconjugate Vaccines: The Regulatory Framework. , 2015, Methods in molecular biology.

[12]  B. Lepenies,et al.  Carbohydrate-Based Vaccines: An Overview. , 2015, Methods in molecular biology.

[13]  Maria Grazia Starita.  The Regulatory Framework , 2012 .