Optimization for the production of a dengue live-attenuated Quadrivalent vaccine in Vero cells grown on microcarriers

IF 2.7 Q3 IMMUNOLOGY

Vaccine: X Pub Date : 2025-05-21 DOI:10.1016/j.jvacx.2025.100658

Shannon Haughney , Seth Clark , Elizabeth Carey , Nelson Lee Afanador , Victoria Stabile , Bernard Kang , Samantha Marrone , Jillian Shingler , Carl Hofmann , Christopher J. Wang , Christopher Ton

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Abstract

Dengue is a mosquito-borne disease and is a major global health threat, especially in tropical and subtropical regions. In this study, we describe the optimization of virus production for a dengue live-attenuated quadrivalent vaccine candidate and demonstrate scalability of a stirred tank bioreactor serum-free microcarrier process. We utilized a design-of-experiment (DoE) methodology to optimize for pH and temperature and evaluate effect of Multiplicity of Infection (MOI) and Time of Infection (TOI) for each serotype during virus production in 2 L and 3 L bioreactors. The optimal pH and temperature for dengue virus production achieved ∼10× higher virus titer at peak virus production for all 4 serotypes compared to baseline condition. Different MOI and TOI did not impact peak virus production. Results from the DoE studies were successfully scaled to the 50 L Single-Use Bioreactor (SUB).

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在微载体上生长的Vero细胞中优化生产登革热减毒四价活疫苗

登革热是一种蚊媒疾病，是一种主要的全球健康威胁，特别是在热带和亚热带地区。在这项研究中，我们描述了登革热四价减毒活疫苗候选病毒生产的优化，并证明了搅拌槽生物反应器无血清微载体工艺的可扩展性。采用实验设计（DoE）方法，在2l和3l生物反应器中优化pH和温度，并评估每种血清型的感染多重性（Multiplicity of Infection， MOI）和感染时间（Time of Infection， TOI）的影响。与基线条件相比，在所有4种血清型中，登革热病毒生产的最佳pH和温度在病毒生产高峰时的病毒滴度提高了约10倍。不同的MOI和TOI对病毒产量峰值没有影响。DoE研究的结果成功地扩展到50 L一次性生物反应器（SUB）。

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