Serogroup quantitation of multivalent polysaccharide and polysaccharide-conjugate meningococcal vaccines from China

Abstract

The active components of most meningococcal vaccines are four antigenic serogroup capsular polysaccharides (A, C, Y, W135). The vaccines, monovalent or multivalent mixtures of either free polysaccharides or polysaccharides conjugated to antigenic carrier proteins, may be in liquid or lyophilised formulations, with or without excipients. Acid hydrolysis and chromatographic methods for serogroup quantitation, which were previously optimised and qualified using polysaccharide-based standards and a narrow range of real vaccines, are here challenged with multiple lots of a broad assortment of additional multivalent polysaccharide-based meningococcal vaccine products. Centrifugal filtration successfully removed all interfering lactose excipient without loss of polysaccharides to allow for the determination of Y and W135 serogroups. Replicate operations by three different analysts indicated high method reproducibility. Results indicated some lot-to-lot and product-to-product variations. However, all vaccines were within general specifications for each serogroup polysaccharide, with the exception of all lots of one polysaccharide vaccine - which by these methods were found to be deficient in the serogroup A component only. These robust techniques are very useful for the evaluation of antigen content and consistency of manufacture. The deformulation, hydrolysis and chromatographic methods may be adaptable for the evaluation of other types of polysaccharide-based vaccines.

Keywords: CP; CV; Capsular polysaccharide; Chinese Pharmacopoeia; EP; European Pharmacopoeia; Gal; Glc; Glycoconjugate; HPAEC-PAD; ManN-6-P; ManNAc-6-P; Meningococcal vaccine; N-acetylmannosamine-6-phosphate; N-acetylneuraminic acid; Neisseria meningitidis; Neu; Neu5Ac; RODI; TT; coefficient of variation; galactose; glucose; high-pH anion-exchange chromatography with pulsed amperometric detection; mannosamine-6-phosphate; neuraminic acid; reverse-osmosis deionised; tetanus toxoid.