Zhang Cheng, Berg Adam, Joe Carina C D, Dalby Paul A, Douglas Alexander D
Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London, WC1E 6BT, United Kingdom.
Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, OX3 7DQ, Oxford, United Kingdom.
NPJ Vaccines. 2023 Jun 5;8(1):85. doi: 10.1038/s41541-023-00674-2.
Distribution of vaccines which require refrigerated or frozen storage can be challenging and expensive. The adenovirus vector platform has been widely used for COVID-19 vaccines while several further candidate vaccines using the platform are in clinical development. In current liquid formulations, adenoviruses require distribution at 2-8 °C. The development of formulations suitable for ambient temperature distribution would be advantageous. Previous peer-reviewed reports of adenovirus lyophilization are relatively limited. Here, we report the development of a formulation and process for lyophilization of simian adenovirus-vectored vaccines based on the ChAdOx1 platform. We describe the iterative selection of excipients using a design of experiments approach, and iterative cycle improvement to achieve both preservation of potency and satisfactory cake appearance. The resulting method achieved in-process infectivity titre loss of around 50%. After drying, there was negligible further loss over a month at 30 °C. Around 30% of the predrying infectivity remained after a month at 45 °C. This performance is likely to be suitable for 'last leg' distribution at ambient temperature. This work may also facilitate the development of other product presentations using dried simian adenovirus-vectored vaccines.
需要冷藏或冷冻储存的疫苗分发可能具有挑战性且成本高昂。腺病毒载体平台已广泛用于新冠疫苗，同时还有几种使用该平台的候选疫苗正在临床开发中。在当前的液体制剂中，腺病毒需要在2-8°C下分发。开发适合常温分发的制剂将具有优势。先前经过同行评审的腺病毒冻干报告相对有限。在此，我们报告了基于ChAdOx1平台的猿猴腺病毒载体疫苗冻干制剂和工艺的开发。我们描述了使用实验设计方法对辅料进行迭代选择，以及通过迭代循环改进来实现效力保存和令人满意的冻干块外观。所得方法在冻干过程中的感染性滴度损失约为50%。干燥后，在30°C下放置一个月，进一步损失可忽略不计。在45°C下放置一个月后，仍保留约30%的冻干前感染性。这种性能可能适用于常温下的“最后一程”分发。这项工作也可能有助于使用干燥的猿猴腺病毒载体疫苗开发其他产品形式。
