Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli.
Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli.
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DOI：
10.1186/s12934-021-01588-1
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发表时间：
2021-05-24
影响因子：
6.4
通讯作者：
Micheletti M
中科院分区：
文献类型：
--
作者：
Samaras JJ;Mauri M;Kay EJ;Wren BW;Micheletti M
蛋白多糖偶联技术(PGCT)使用经过专门修饰的细菌细胞来生产重组糖结合疫苗。该疫苗平台在这方面具有巨大的潜力，即由于其模块化的性质，与传统的化学结合方法相比简化了生产过程，并且易于扩大操作。因此，生产时间和成本预计将大幅减少，使PGCT制造的疫苗成为适合中低收入国家的疫苗技术，这些国家的疫苗覆盖率仍然很低，而且不稳定。这项工作旨在开发一个集成的全程自动化平台，用于筛选PGCT制造的糖结合疫苗候选。成功地将糖共轭生产的小试过程转化为微规模的自动化装置。它与数值计算软件集成在一起，允许免提操作和一个在生产过程中适应生物变化的平台。通过技术和生物复制证明了平台的稳健性，随后该平台被用于筛选生产4型肺炎球菌候选疫苗的最有利条件。这项工作建立了一个有效的自动化平台，能够识别最合适的大肠杆菌菌株和基因结构，用于正在进行的早期研究，并进一步纳入临床前试验。网上版载有补充材料，可在10.1186/s12934-021-01588-1查阅。
Protein Glycan Coupling Technology (PGCT) uses purposely modified bacterial cells to produce recombinant glycoconjugate vaccines. This vaccine platform holds great potential in this context, namely due to its modular nature, the simplified production process in comparison to traditional chemical conjugation methods, and its amenability to scaled-up operations. As a result, a considerable reduction in production time and cost is expected, making PGCT-made vaccines a suitable vaccine technology for low-middle income countries, where vaccine coverage remains predominantly low and inconsistent. This work aims to develop an integrated whole-process automated platform for the screening of PGCT-made glycoconjugate vaccine candidates. The successful translation of a bench scale process for glycoconjugate production to a microscale automated setting was achieved. This was integrated with a numerical computational software that allowed hands-free operation and a platform adaptable to biological variation over the course of a production process. Platform robustness was proven with both technical and biological replicates and subsequently the platform was used to screen for the most favourable conditions for production of a pneumococcal serotype 4 vaccine candidate. This work establishes an effective automated platform that enabled the identification of the most suitable E. coli strain and genetic constructs to be used in ongoing early phase research and be further brought into preclinical trials. The online version contains supplementary material available at 10.1186/s12934-021-01588-1.
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影响因子：
3.5
作者：
Ihssen, Julian;Kowarik, Michael;Thoeny-Meyer, Linda
通讯作者：
Thoeny-Meyer, Linda
影响因子：
15.3
作者：
Avery, OT;Goebel, WF
通讯作者：
Goebel, WF
DOI：
10.1016/s0140-6736(17)32149-9
发表时间：
2017-12-02
期刊：
Lancet (London, England)
影响因子：
--
作者：
Jin C;Gibani MM;Moore M;Juel HB;Jones E;Meiring J;Harris V;Gardner J;Nebykova A;Kerridge SA;Hill J;Thomaides-Brears H;Blohmke CJ;Yu LM;Angus B;Pollard AJ
通讯作者：
Pollard AJ
影响因子：
5.8
作者：
Kay EJ;Yates LE;Terra VS;Cuccui J;Wren BW
通讯作者：
Wren BW
影响因子：
9.2
作者：
Reglinski M;Ercoli G;Plumptre C;Kay E;Petersen FC;Paton JC;Wren BW;Brown JS
通讯作者：
Brown JS