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Effect of Shear Stresses on Adenovirus Activity and Aggregation during Atomization To Produce Thermally Stable Vaccines by Spray Drying
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-06-01 , DOI: 10.1021/acsbiomaterials.0c00317 Blair A. Morgan 1 , Myla Manser 1 , Mangalakumari Jeyanathan 2 , Zhou Xing 2 , Emily D. Cranston 1, 3, 4 , Michael R. Thompson 1
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-06-01 , DOI: 10.1021/acsbiomaterials.0c00317 Blair A. Morgan 1 , Myla Manser 1 , Mangalakumari Jeyanathan 2 , Zhou Xing 2 , Emily D. Cranston 1, 3, 4 , Michael R. Thompson 1
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Considering the substantive potential benefits of thermally stable dry powder vaccines to public health, causes for inactivation of their sensitive viral vectors during preparation require intensive study. The focus of this work was atomization of suspensions containing encapsulating excipients and a human type 5 adenovirus, involving a detailed investigation of shear stresses in the nozzle of a spray dryer. Samples were sprayed at 25 °C into falcon tubes and immediately evaluated for viral activity by in vitro testing, minimizing the confounding of thermal effects on the deactivation of the virus, although interfacial stresses could not be decoupled from shear stresses. Despite the expectations of only virus deactivation with ever-increasing shear stresses in the spray nozzle, some conditions were found to show better activity than the positive control, leading to investigations of viral aggregation. It was found that the adenovirus experienced minor aggregation when mixed with the excipient solutions, which was reversed by subjecting samples to moderate shear conditions in the spray nozzle. At very high shear rates, the activity diminished again because of damage to the viral capsid fibers, which also led to the production of new aggregates after atomization. Despite these findings, activity losses caused by shear were small compared to the overall spray drying process loss. However, formulation composition, solution viscosity, and process conditions should be considered carefully for optimization because of their impact on aggregation. This is the first known report comparing shear, aggregation, and biological activity loss during the atomization step of spray drying viral vaccines.
中文翻译：
剪切应力对喷雾干燥产生热稳定疫苗的雾化过程中腺病毒活性和聚集的影响
考虑到热稳定的干粉疫苗对公共卫生的实质性潜在好处，在制备过程中其敏感病毒载体失活的原因需要深入研究。这项工作的重点是雾化包含包囊赋形剂和人5型腺病毒的悬浮液，包括对喷雾干燥器喷嘴中的剪切应力进行详细研究。将样品在25°C的温度下喷入猎鹰管中，并通过体外测试立即评估其病毒活性，从而最大程度地降低了对病毒灭活的热效应造成的混淆，尽管不能将界面应力与剪切应力分离。尽管期望只有病毒灭活，并且喷嘴中的切应力不断增加，发现某些条件显示出比阳性对照更好的活性，从而导致了对病毒聚集的研究。已经发现，当与赋形剂溶液混合时，腺病毒会发生较小的聚集，这通过在喷嘴中对样品进行中等剪切条件来逆转。在很高的剪切速率下，由于病毒衣壳纤维的损坏，活性再次降低，这也导致了雾化后新聚集体的产生。尽管有这些发现，但与整体喷雾干燥过程的损失相比，剪切造成的活性损失很小。但是，应仔细考虑配方组成，溶液粘度和工艺条件以进行优化，因为它们会影响聚集。这是第一个比较剪切，聚集，
更新日期：2020-07-13
中文翻译：
剪切应力对喷雾干燥产生热稳定疫苗的雾化过程中腺病毒活性和聚集的影响
考虑到热稳定的干粉疫苗对公共卫生的实质性潜在好处，在制备过程中其敏感病毒载体失活的原因需要深入研究。这项工作的重点是雾化包含包囊赋形剂和人5型腺病毒的悬浮液，包括对喷雾干燥器喷嘴中的剪切应力进行详细研究。将样品在25°C的温度下喷入猎鹰管中，并通过体外测试立即评估其病毒活性，从而最大程度地降低了对病毒灭活的热效应造成的混淆，尽管不能将界面应力与剪切应力分离。尽管期望只有病毒灭活，并且喷嘴中的切应力不断增加，发现某些条件显示出比阳性对照更好的活性，从而导致了对病毒聚集的研究。已经发现，当与赋形剂溶液混合时，腺病毒会发生较小的聚集，这通过在喷嘴中对样品进行中等剪切条件来逆转。在很高的剪切速率下，由于病毒衣壳纤维的损坏，活性再次降低，这也导致了雾化后新聚集体的产生。尽管有这些发现，但与整体喷雾干燥过程的损失相比，剪切造成的活性损失很小。但是，应仔细考虑配方组成，溶液粘度和工艺条件以进行优化，因为它们会影响聚集。这是第一个比较剪切，聚集，
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