Addressing the Cold Reality of mRNA Vaccine Stability.
Addressing the Cold Reality of mRNA Vaccine Stability.
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解决信使核糖核酸疫苗稳定性的冷现实。
DOI：
10.1016/j.xphs.2020.12.006
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Mastrobattista E
中科院分区：
文献类型：
--
作者：
Crommelin DJA;Anchordoquy TJ;Volkin DB;Jiskoot W;Mastrobattista E
随着 mRNA 疫苗成为抗击 COVID-19 大流行的后期临床试验的领跑者，围绕其配方和稳定性的挑战变得显而易见。在这篇评论中，我们首先根据现有的公开信息描述了公司关于在整个疫苗供应链中（冷冻）储存 mRNA 疫苗药品的建议。然后，我们回顾了有关 mRNA 候选疫苗药物稳定性的文献，包括提高其稳定性的尝试、监测其稳定性的分析技术以及涵盖产品表征和储存稳定性的监管指南。我们的结论是，目前缺乏确定 mRNA 候选疫苗关键理化降解机制的系统方法。因此，在冷藏或环境温度下储存、运输和给药期间合理设计最佳稳定的 mRNA 疫苗制剂应该成为药物开发界的首要任务。除了针对多种病毒病原体的人类免疫原性证据（包括针对 COVID-19 的令人信服的功效结果）之外，mRNA 疫苗方法的另一个关键优势是它很容易适应快速应对未来新发传染病的爆发。因此，我们不应等到下一次大流行才解决与配制 mRNA 疫苗的稳定性和储存相关的挑战。
As mRNA vaccines became the frontrunners in late-stage clinical trials to fight the COVID-19 pandemic, challenges surrounding their formulation and stability became readily apparent. In this commentary, we first describe company proposals, based on available public information, for the (frozen) storage of mRNA vaccine drug products across the vaccine supply chain. We then review the literature on the pharmaceutical stability of mRNA vaccine candidates, including attempts to improve their stability, analytical techniques to monitor their stability, and regulatory guidelines covering product characterization and storage stability. We conclude that systematic approaches to identify the key physicochemical degradation mechanism(s) of formulated mRNA vaccine candidates are currently lacking. Rational design of optimally stabilized mRNA vaccine formulations during storage, transport, and administration at refrigerated or ambient temperatures should thus have top priority in the pharmaceutical development community. In addition to evidence of human immunogenicity against multiple viral pathogens, including compelling efficacy results against COVID-19, another key strength of the mRNA vaccine approach is that it is readily adaptable to rapidly address future outbreaks of new emerging infectious diseases. Consequently, we should not wait for the next pandemic to address and solve the challenges associated with the stability and storage of formulated mRNA vaccines.
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影响因子：
9.2
作者：
Lutz J;Lazzaro S;Habbeddine M;Schmidt KE;Baumhof P;Mui BL;Tam YK;Madden TD;Hope MJ;Heidenreich R;Fotin-Mleczek M
通讯作者：
Fotin-Mleczek M
DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
3.8
作者：
Stitz L;Vogel A;Schnee M;Voss D;Rauch S;Mutzke T;Ketterer T;Kramps T;Petsch B
通讯作者：
Petsch B
DOI：
10.1007/978-1-4939-6481-9_13
发表时间：
2017-01-01
期刊：
RNA VACCINES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Hinz, Thomas;Kallen, Kajo;Kalinke, Ulrich
通讯作者：
Kalinke, Ulrich
影响因子：
2.7
作者：
Jones, Kathryn L.;Drane, Debbie;Gowans, Eric J.
通讯作者：
Gowans, Eric J.