疫苗安全性视角下的肺炎链球菌荚膜多糖制备工艺研究进展

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

摘要:

肺炎链球菌疫苗在防御由肺炎链球菌引发的各类侵袭性与非侵袭性疾病中扮演着不可或缺的角色，荚膜多糖作为关键抗原成分，杂质残留直接造成了肺炎多糖疫苗以及多糖结合疫苗在临床使用中的不良反应。随着全球对涵盖广泛血清型的高价肺炎链球菌疫苗需求的持续增长，研发高效、高纯度且可大规模生产的荚膜多糖抗原技术愈发显得紧迫且至关重要。荚膜多糖的质量属性受到多维度因素的交互影响，涵盖了病原菌株的选择、培养基配方、发酵过程调控以及纯化技术等诸多环节。遵循质量源于设计(quality by design,QbD)的质量管理理念与工艺开发路径，本文系统性总结了从上游菌株筛选优化、精细化发酵工艺设计，直到下游纯化技术的全过程的知识与经验，旨在为构建和完善荚膜多糖生产工艺体系提供理论指导与实践策略。

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.