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

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 con...

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Autores principales: Samaras, Jasmin J., Mauri, Marta, Kay, Emily J., Wren, Brendan W., Micheletti, Martina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142613/
https://www.ncbi.nlm.nih.gov/pubmed/34030723
http://dx.doi.org/10.1186/s12934-021-01588-1
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author Samaras, Jasmin J.
Mauri, Marta
Kay, Emily J.
Wren, Brendan W.
Micheletti, Martina
author_facet Samaras, Jasmin J.
Mauri, Marta
Kay, Emily J.
Wren, Brendan W.
Micheletti, Martina
author_sort Samaras, Jasmin J.
collection PubMed
description 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. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-021-01588-1.
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spelling pubmed-81426132021-05-25 Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli Samaras, Jasmin J. Mauri, Marta Kay, Emily J. Wren, Brendan W. Micheletti, Martina Microb Cell Fact Research 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. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-021-01588-1. BioMed Central 2021-05-24 /pmc/articles/PMC8142613/ /pubmed/34030723 http://dx.doi.org/10.1186/s12934-021-01588-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Samaras, Jasmin J.
Mauri, Marta
Kay, Emily J.
Wren, Brendan W.
Micheletti, Martina
Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title_full Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title_fullStr Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title_full_unstemmed Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title_short Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
title_sort development of an automated platform for the optimal production of glycoconjugate vaccines expressed in escherichia coli
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142613/
https://www.ncbi.nlm.nih.gov/pubmed/34030723
http://dx.doi.org/10.1186/s12934-021-01588-1
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