Roberts Peter L, Lloyd David
Bio Products Laboratory, Dagger Lane, Elstree, Hertfordshire, UK.
Biologicals. 2007 Oct;35(4):343-7. doi: 10.1016/j.biologicals.2007.02.005. Epub 2007 May 24.
Virus inactivation by a number of protein denaturants commonly used in gel affinity chromatography for protein elution and gel recycling has been investigated. The enveloped viruses Sindbis, herpes simplex-1 and vaccinia, and the non-enveloped virus polio-1 were effectively inactivated by 0.5 M sodium hydroxide, 6 M guanidinium thiocyanate, 8 M urea and 70% ethanol. However, pH 2.6, 3 M sodium thiocyanate, 6 M guanidinium chloride and 20% ethanol, while effectively inactivating the enveloped viruses, did not inactivate polio-1. These studies demonstrate that protein denaturants are generally effective for virus inactivation but with the limitation that only some may inactivate non-enveloped viruses. The use of protein denaturants, together with virus reduction steps in the manufacturing process should ensure that viral cross contamination between manufacturing batches of therapeutic biological products is prevented and the safety of the product ensured.
人们研究了多种常用于凝胶亲和色谱法中蛋白质洗脱和凝胶回收的蛋白质变性剂对病毒的灭活作用。包膜病毒辛德毕斯病毒、单纯疱疹病毒1型和痘苗病毒，以及非包膜病毒脊髓灰质炎病毒1型可被0.5M氢氧化钠、6M硫氰酸胍、8M尿素和70%乙醇有效灭活。然而，pH2.6、3M硫氰酸钠、6M氯化胍和20%乙醇虽然能有效灭活包膜病毒，但不能灭活脊髓灰质炎病毒1型。这些研究表明，蛋白质变性剂通常对病毒灭活有效，但存在局限性，即只有一些变性剂能灭活非包膜病毒。在生产过程中使用蛋白质变性剂并结合病毒去除步骤，应能确保防止治疗性生物制品生产批次之间的病毒交叉污染，并确保产品的安全性。
