Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation.
Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation.
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DOI：
10.1038/s41598-021-00065-4
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发表时间：
2021-10-22
影响因子：
4.6
通讯作者：
Douglas AD
中科院分区：
文献类型：
--
作者：
Dulal P;Gharaei R;Berg A;Walters AA;Hawkins N;Claridge TDW;Kowal K;Neill S;Ritchie AJ;Ashfield R;Hill AVS;Tronci G;Russell SJ;Douglas AD
腺病毒载体为疫苗开发提供了平台技术。该平台的价值在2019冠状病毒病大流行期间得到了证明。虽然2-8°C的良好稳定性是该平台的优势，但非冷链分销将具有实质性优势，特别是在低收入国家。我们之前报道过一种新的、可能更便宜的热稳定方法，使用单糖和玻璃微纤维基质的组合，在高达45°C的温度下储存腺病毒载体疫苗后，实现了极好的恢复。然而，这种基质容易碎裂，因此不适合临床翻译。在这里，我们报告了一项可能适合临床使用的替代纤维基质的研究。许多商业上可用的基质允许良好的蛋白质回收率，糖玻璃的质量和干燥产品的水分含量，但没有达到原始玻璃纤维基质的热稳定性能。因此，我们进一步研究了玻璃纤维基质及其组分的物理和化学特性，发现玻璃纤维基质中存在的聚乙烯醇有助于疫苗的稳定性。这一发现使我们能够确定具有良好性能的潜在生物相容性基质。我们讨论了将该技术转化为临床应用所面临的挑战，包括工艺性能的可靠性。
Adenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2–8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.
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