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

HANDLE オープンアクセス

抄録

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

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.

収録刊行物

  • Cytotechnology

    Cytotechnology 2023-10-27

    Springer Science and Business Media B.V.

詳細情報 詳細情報について

  • CRID
    1050018218945970944
  • ISSN
    15730778
    09209069
  • HANDLE
    11094/93282
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB

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