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ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Industrial Biotechnology
Volume 12 - 2024 |
doi: 10.3389/fbioe.2024.1451881
Novel manufacturing process of pneumococcal capsular polysaccharides using advanced sterilization methods
Provisionally accepted- 1 Beijing Minhai Biotechnology Co. Ltd, Beijing, China
- 2 Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China
Pneumococcal disease is caused by Streptococcus pneumoniae, including pneumonia, meningitis and sepsis. Capsular polysaccharides (CPSs) have been shown as effective antigens to stimulate protective immunity against pneumococcal disease. A major step in the production of pneumococcal vaccines is to prepare CPSs that meet strict quality standards in immunogenicity and safety. The major impurities come from bacterial proteins, nucleic acids and cell wall polysaccharides. Traditionally, the impurity level of refined CPSs is reduced by optimization of purification process. In this study, we investigated new aeration strategy and advanced sterilization methods by formaldehyde or β-propiolactone (BPL) to increase the amount of soluble polysaccharide in fermentation supernatant and to prevent bacterial lysis during inactivation. Furthermore, we developed a simplified process for the CPS purification, which involves ultrafiltration and diafiltration, followed by acid and alcohol precipitation, and finally diafiltration and lyophilization to obtain pure polysaccharide. The CPSs prepared from formaldehyde and BPL sterilization contained significantly lower level of residual impurities compared to the refined CPSs obtained from traditional deoxycholate sterilization. Finally, we showed that this novel approach of CPS preparation can be scaled up for polysaccharide vaccine production.
Keywords: capsular polysaccharide, sterilization agent, purification, impurity, Phase Variation
Received: 20 Jun 2024; Accepted: 22 Jul 2024.
Copyright: © 2024 Li, Cao, Huang, Liu, Wang, Jin, Liu, Zhang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xin Cao, Beijing Minhai Biotechnology Co. Ltd, Beijing, China
Xueting Huang, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, 100084, China
Yanli Liu, Beijing Minhai Biotechnology Co. Ltd, Beijing, China
Qian Jin, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, 100084, China
Jiankai Liu, Beijing Minhai Biotechnology Co. Ltd, Beijing, China
Jingren Zhang, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, 100084, China
Haifa Zheng, Beijing Minhai Biotechnology Co. Ltd, Beijing, China
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