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Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli

Samaras, JJ; Mauri, M; Kay, EJ; Wren, BW; Micheletti, M; (2021) Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli. Microbial Cell Factories , 20 (1) , Article 104. 10.1186/s12934-021-01588-1. Green open access

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Abstract

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.

Type: Article
Title: Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12934-021-01588-1
Publisher version: https://doi.org/10.1186/s12934-021-01588-1
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Automation, Bioconjugation, Glycoconjugate vaccine, Glycoengineering, Glycoprotein, High throughput process development, PGCT, Pneumococcal vaccine, Screening studies
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10128724
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