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Development of a high-yield live-virus vaccine production platform using a novel fixed-bed bioreactor
Vaccine ( IF 4.5 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.vaccine.2020.03.041
Dalton M. Berrie , Robin C. Waters , Christopher Montoya , Alex Chatel , Eric M. Vela

The increasing importance of viral vaccine manufacturing has driven the need for high cell density process optimization that allows for higher production levels. Vero cells are one of the more popular adherent cell lines used for viral vaccine production. However, production is limited due to the logistical limitations surrounding adherent cell line processes, such as large equipment footprints, time and labor-intensive processes, and larger costs per dose. We have addressed this limitation with the establishment of a viral vaccine production system utilizing the novel single use scale-X™ carbo bioreactor. The unit is compact and is scalable and one of the novel features of the system is the continuous in-line downstream purification and concentration processes associated with the bioreactor vessel. We present the results from a campaign featuring a proprietary Vero cell line for production of a live recombinant Vesicular stomatitis virus vaccine that features the Lassa Fever virus glycoproteins. Metabolite analyses and viral yield comparison between traditional flasks, cell factories, and the scale-X carbo bioreactor were performed, and on average, the single use bioreactor produced 2–4 logs higher titers per surface area, approximately 5 × 1010 pfu/cm2, compared to classical flatstock, 2.67 × 106 pfu/cm2, and cell factories production, 5.77 × 108 pfu/cm2. Overall, we describe a novel bioreactor platform that allows for a cost-efficient and scalable process for viral vaccine production.



中文翻译:

使用新型固定床生物反应器开发高产量活病毒疫苗生产平台

病毒疫苗生产的重要性日益提高,因此需要高细胞密度的工艺优化,以实现更高的生产水平。Vero细胞是用于生产病毒疫苗的最受欢迎的贴壁细胞系之一。然而,由于围绕贴壁细胞系过程的后勤限制,例如大的设备占地面积,时间和劳动密集的过程以及每剂更大的成本,生产受到限制。我们已经通过建立利用新型一次性使用scale-X™碳生物反应器的病毒疫苗生产系统解决了这一限制。该单元紧凑且可扩展,该系统的新颖特征之一是与生物反应器容器相关的连续在线下游纯化和浓缩过程。我们介绍了一项运动的成果,该运动的特点是拥有专有的Vero细胞系,可生产具有拉萨热病毒病毒糖蛋白的活重组水泡性口炎病毒疫苗。进行了传统烧瓶,细胞工厂和scale-X碳生物反应器之间的代谢物分析和病毒产量比较,平均而言,一次性生物反应器每表面积产生的滴度高2-4个对数,大约5×1010 pfu / cm 2,相比之下,传统的扁平纸为2.67×10 6 pfu / cm 2,而电池工厂的产量为5.77×10 8 pfu / cm 2。总体而言,我们描述了一种新型生物反应器平台,该平台可为病毒疫苗生产提供经济高效且可扩展的过程。

更新日期:2020-04-03
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