Abstract

The novel influenza A virus (IAV) defective interfering particle “OP7” inhibits IAV replication in a co-infection and was previously suggested as a promising antiviral agent. Here, we report a batch-mode cell culture-based production process for OP7. In the present study, a seed virus containing standard virus (STV) and OP7 was used. The yield of OP7 strongly depended on the production multiplicity of infection. To inactivate infectious STV in the OP7 material, which may cause harm in a potential application, UV irradiation was used. The efficacy of OP7 in this material was preserved, as shown by an in vitro interference assay. Next, steric exclusion chromatography was used to purify and to concentrate (~ 13-fold) the UV-treated material. Finally, administration of produced OP7 material in mice did not show any toxic effects. Furthermore, all mice infected with a lethal dose of IAV survived the infection upon OP7 co-treatment. Thus, the feasibility of a production workflow for OP7 and its potential for antiviral treatment was demonstrated.

Key points

• OP7 efficacy strongly depended on the multiplicity of infection used for production

• Purification by steric exclusion chromatography increased OP7 efficacy

• OP7-treated mice were protected against a lethal infection with IAV

中文翻译：

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OP7，一种新型的甲型流感病毒缺陷型干扰颗粒：具有抗病毒潜力的生产，纯化和动物实验

摘要

新型甲型流感病毒（IAV）缺陷干扰颗粒“ OP7”在共感染中抑制IAV复制，以前被认为是有前途的抗病毒剂。在这里，我们报告OP7的基于批处理模式的细胞培养生产过程。在本研究中，使用了包含标准病毒（STV）和OP7的种子病毒。OP7的产量在很大程度上取决于感染的生产多样性。为了使OP7材料中的感染性STV灭活（可能在潜在的应用中造成伤害），使用了紫外线照射。如体外实验所示，保留了OP7在该材料中的功效干扰测定。接下来，使用空间排阻色谱法纯化并浓缩（约13倍）UV处理的材料。最后，在小鼠中施用产生的OP7材料没有显示任何毒性作用。此外，所有感染了致死剂量IAV的小鼠在OP7联合治疗后均存活下来。因此，证明了OP7生产工作流程的可行性及其抗病毒治疗的潜力。

关键点

•OP7的功效在很大程度上取决于生产中使用的感染复数

•通过空间排阻色谱法纯化可提高OP7效力

•OP7处理的小鼠受到IAV的致命感染保护