Lyophilization to enable distribution of ChAdOx1 and ChAdOx2 adenovirus-vectored vaccines without refrigeration.
Lyophilization to enable distribution of ChAdOx1 and ChAdOx2 adenovirus-vectored vaccines without refrigeration.
复制标题
DOI：
10.1038/s41541-023-00674-2
复制
发表时间：
2023-06-05
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
需要冷藏或冷冻储存的疫苗的分配可能具有挑战性且昂贵。腺病毒载体平台已广泛用于COVID-19疫苗，而使用该平台的几种其他候选疫苗正在临床开发中。在目前的液体制剂中，腺病毒需要在2-8 °C下分布。开发适合环境温度分布的配方将是有利的。以前的同行评议报告的腺病毒冻干是相对有限的。在这里，我们报告了一种基于ChAdOx 1平台的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的赋形剂的迭代选择，以及迭代循环改进，以实现效价的保持和令人满意的饼外观。所得方法实现了约50%的过程中感染性滴度损失。干燥后，在30 °C下一个月内的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%的预干燥感染性。这种性能很可能适用于环境温度下的“最后一段”分布。这项工作也可能促进其他产品介绍使用干燥的猿猴腺病毒载体疫苗的发展。
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.
登录
查看更多内容
影响因子：
3.8
作者：
Grant, Yitzchak;Matejtschuk, Paul;Dalby, Paul A.
通讯作者：
Dalby, Paul A.
影响因子：
5.1
作者：
Croyle, MA;Cheng, X;Wilson, JM
通讯作者：
Wilson, JM
DOI：
10.1016/s2666-5247(22)00126-4
发表时间：
2022-09
期刊：
The Lancet. Microbe
影响因子：
--
作者：
Jenkin D;Ritchie AJ;Aboagye J;Fedosyuk S;Thorley L;Provstgaad-Morys S;Sanders H;Bellamy D;Makinson R;Xiang ZQ;Bolam E;Tarrant R;Ramos Lopez F;Platt A;Poulton I;Green C;Ertl HCJ;Ewer KJ;Douglas AD
通讯作者：
Douglas AD
影响因子：
12.4
作者：
Croyle, MA;Cheng, X;Wilson, JM
通讯作者：
Wilson, JM
影响因子：
5.5
作者：
Kristensen D;Giersing B;Hickling J;Kazi F;Scarna T;Kahn AL;Hsu V;Gandrup-Marino K;Menozzi-Arnaud M
通讯作者：
Menozzi-Arnaud M