Research progress in the manufacturing process of Streptococcus pneumoniae capsular polysaccharide from the perspective of vaccine safety

Abstract:

The pneumococcal vaccines play an indispensable role in defending against various invasive and non-invasive diseases caused by Streptococcus pneumoniae.The capsular polysaccharide is a key antigen,while the impurity residues in the capsular polysaccharide cause side effects of pneumococcal polysaccharide vaccines and conjugate vaccines.As the global demand for high-valent pneumococcal vaccines covering a wide range of serotypes keeps increasing,it is urgent and crucial to develop efficient and scalable production technologies for high-purity capsular polysaccharide antigens.The safety and quality attributes of capsular polysaccharide are influenced by multiple factors encompassing the selection of pathogen strains,formulation of culture media,control of fermentation processes,and purification technologies.Following the concept of Quality by Design (QbD) and the process development path,this article systematically summarizes the knowledge and experience throughout the entire process ranging from upstream strain screening and optimization,refined fermentation process design,to downstream purification,aiming to provide comprehensive and in-depth theoretical guidance and practical strategies for building and improving the production system of capsular polysaccharide.

Key words:pneumococcal vaccine;capsular polysaccharide;antigen;quality;impurities