Polysaccharide-based vaccines are available for the prevention of disease caused by certain pathogens.  For children under 2 years of age, purified polysaccharide vaccines are relatively ineffective due to the infant's naive immune system.  Polysaccharide-conjugate vaccines have been developed to circumvent this problem. There are many ways to covalently link polysaccharides to carrier proteins, e.g., direct coupling or use of bi-functional linker chemistries. We studied the covalent attachment of polysaccharide antigens onto a protein carrier using reductive amination under aqueous condition.  Conjugation reaction parameters were evaluated for their effect on reaction efficiency and conjugate attributes, such as conjugate size and conjugate polysaccharide-to-protein ratio. Reaction parameters included polysaccharide concentration, polysaccharide-to-protein reaction charge ratio, polysaccharide activation level and molecular weight, reaction pH and ionic strength, and conjugation time. High throughput tools were employed to increase process robustness while minimizing resources and cycle time.  Using these results, empirically-derived mathematical models are developed to provide a better understanding of the conjugation reaction.

Process optimization for a polysaccharide-protein conjugate vaccine: Correlating process parameters to product attributes

247th National Meeting (2014)

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