Mathematical Model for Measles Virus Production in Batch Bioreactors.

IF 3.5 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-07-17 DOI:10.1002/bit.70017

Shiny Samuel,Todd Przybycien

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引用次数: 0

Abstract

Measles virus (MeV) is a promising vector for vaccines, gene therapy, and oncolytic virus therapy due to its safety, efficacy, and natural ability to target tumor cells. However, MeV production in bioreactors, typically with microcarrier cultures of Vero cells, is challenging because of the sensitivity of the virus to temperature, shear stress, and low pH. At 37°C, the optimal growth temperature of Vero cells, MeV has a short half-life of 1 h, requiring precise control of the harvest time (TOH) to maximize yield. We developed a mathematical model to predict the TOH for recombinant MeV production in Vero cells. Model predictions for TOH were in good agreement with observations across five separate bioreactor runs, despite significant run-to-run performance variations. Parameter analysis revealed that virus attachment parameters and thermal degradation rate significantly influence infection dynamics. Furthermore, the model highlights the critical importance of accurately characterizing seed virus quality, particularly concerning defective interfering particle (DIP) content, to minimize production variability and optimize yield.

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间歇式生物反应器中麻疹病毒生产的数学模型。

麻疹病毒（MeV）因其安全性、有效性和天然靶向肿瘤细胞的能力而成为疫苗、基因治疗和溶瘤病毒治疗的一种有前景的载体。然而，在生物反应器中生产MeV，通常是用微载体培养的Vero细胞，具有挑战性，因为病毒对温度、剪切应力和低ph值敏感。在37°C （Vero细胞的最佳生长温度）下，MeV的半衰期很短，只有1小时，需要精确控制收获时间（TOH）以最大化产量。我们建立了一个数学模型来预测重组MeV在Vero细胞中产生的TOH。模型对TOH的预测与五个单独的生物反应器运行的观察结果很好地吻合，尽管运行之间的性能存在显著差异。参数分析表明，病毒附着参数和热降解率对感染动力学有显著影响。此外，该模型强调了准确表征种子病毒质量的重要性，特别是关于缺陷干扰颗粒（DIP）含量，以最大限度地减少生产变异性并优化产量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

期刊介绍： Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.