Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells

Xing, Zhou; Nguyen, Thao Bich; Kanai-Bai, Guirong; Yamano-Adachi, Noriko; Omasa, Takeshi

doi:https://doi.org/10.1007/s10616-023-00598-8

Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells

Xing, Zhou; Nguyen, Thao Bich; Kanai-Bai, Guirong et al.

Cytotechnology, 2023, 76, 69-83

Number of Access:368（2025-08-15 22:51 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93282

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Title	Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells
Creator	CreatorName Xing, Zhou
	CreatorName Nguyen, Thao Bich
	CreatorName Kanai-Bai, Guirong
	CreatorName Yamano-Adachi, Noriko
	NRID 1000000252586 1000000252586 ORCID 0000-0003-0635-3862 0000-0003-0635-3862 researchmap permalink omasa omasa Scopus Author ID 7003926741 7003926741 CreatorName Omasa, Takeshi
Subject	Bioprocess modeling
	Chinese hamster ovary cell culture
	Process optimization
	Vaccine production
	Virus-like particle
Description	The version of record of this article, first published in Cytotechnology, is available online at Publisher’s website: https://doi.org/10.1007/s10616-023-00598-8
Abstract	Bioprocess development benefits from kinetic models in many aspects, including scale-up, optimization, and process understanding. However, current models are unable to simulate the production process of a coxsackievirus A6 (CVA6) virus-like particle (VLP) vaccine using Chinese hamster ovary cell culture. In this study, a novel kinetic model was constructed, correlating (1) cell growth, death, and lysis kinetics, (2) metabolism of major metabolites, and (3) CVA6 VLP production. To construct the model, two batches of a laboratory-scale 2 L bioreactor cell culture were prepared and various pH shift strategies were applied to examine the effect of pH shift. The proposed model described the experimental data under various conditions with high accuracy and quantified the effect of pH shift. Next, cell culture performance with various pH shift timings was predicted by the calibrated model. A trade-off relationship was found between product yield and quality. Consequently, multiple objective optimization was performed by integrating desirability methodology with model simulation. Finally, the optimal operating conditions that balanced product yield and quality were predicted. In general, the proposed model improved the process understanding and enabled in silico process development of a CVA6 VLP vaccine.
Publisher	Springer Science and Business Media B.V.
Source Title	Cytotechnology
Volume (Issue)	76
Page	69-83
Date of Issued	2023-10-27
Language	English
Handle URL	https://hdl.handle.net/11094/93282
PISSN	09209069
eISSN	15730778
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s10616-023-00598-8
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Cytotechnology. 2023, 76, p. 69-83
DC.title	Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells
DC.creator	Xing, Zhou
	Nguyen, Thao Bich
	Kanai-Bai, Guirong
	Yamano-Adachi, Noriko
	Omasa, Takeshi
DC.publisher	Springer Science and Business Media B.V.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-10-27
DC.identifier	https://doi.org/10.1007/s10616-023-00598-8
DC.subject	Bioprocess modeling
	Chinese hamster ovary cell culture
	Process optimization
	Vaccine production
	Virus-like particle
DC.description	The version of record of this article, first published in Cytotechnology, is available online at Publisher’s website: https://doi.org/10.1007/s10616-023-00598-8
DCTERMS.abstract	Bioprocess development benefits from kinetic models in many aspects, including scale-up, optimization, and process understanding. However, current models are unable to simulate the production process of a coxsackievirus A6 (CVA6) virus-like particle (VLP) vaccine using Chinese hamster ovary cell culture. In this study, a novel kinetic model was constructed, correlating (1) cell growth, death, and lysis kinetics, (2) metabolism of major metabolites, and (3) CVA6 VLP production. To construct the model, two batches of a laboratory-scale 2 L bioreactor cell culture were prepared and various pH shift strategies were applied to examine the effect of pH shift. The proposed model described the experimental data under various conditions with high accuracy and quantified the effect of pH shift. Next, cell culture performance with various pH shift timings was predicted by the calibrated model. A trade-off relationship was found between product yield and quality. Consequently, multiple objective optimization was performed by integrating desirability methodology with model simulation. Finally, the optimal operating conditions that balanced product yield and quality were predicted. In general, the proposed model improved the process understanding and enabled in silico process development of a CVA6 VLP vaccine.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93282
citation_title	Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells
citation_author	Xing, Zhou
	Nguyen, Thao Bich
	Kanai-Bai, Guirong
	Yamano-Adachi, Noriko
	Omasa, Takeshi
citation_publisher	Springer Science and Business Media B.V.
citation_language	English
citation_date	2023-10-27
citation_journal_title	Cytotechnology
citation_volume	76
citation_firstpage	69
citation_lastpage	83
citation_doi	https://doi.org/10.1007/s10616-023-00598-8
citation_public_url	https://hdl.handle.net/11094/93282

Construction of a novel kinetic model for the production process of a CVA6 VLP vaccine in CHO cells

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