mRNA疫苗稳定性研究进展与挑战
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作者单位:

1扬州大学兽医学院/江苏省动物重要疫病与人兽共患病防控协同创新中心,扬州225009;2农业微生物资源发掘与利用全国重点实验室/湖北洪山实验室/预防兽医学湖北省重点实验室/ 华中农业大学动科动医学院,武汉430070

作者简介:

万加武,E-mail:jwwan@yzu.edu.cn

通讯作者:

赵凌,E-mail:lingzhao@mail.hzau.edu.cn
刘爵,E-mail:liujue@263.net

中图分类号:

R392.1

基金项目:

国家自然科学基金联合基金项目(U24A20449);国家自然科学基金重点项目(32430105)


Advances and challenges in stability of mRNA vaccines
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1College of Veterinary Medicine,Yangzhou University/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Yangzhou University, Yangzhou 225009,China;2National Key Laboratory of Agricultural Microbiology/Hubei Hongshan Laboratory/ Key Laboratory of Preventive Veterinary Medicine of Hubei Province/ College of Veterinary Medicine,Huazhong Agricultural University,Wuhan 430070,China

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    摘要:

    作为一种新兴的核酸疫苗技术,mRNA疫苗自新冠疫情以来取得了快速发展并实现了商业化应用。由于其设计灵活、研发周期短,且能够同时诱导体液免疫和细胞免疫应答,该技术已成为传染病防控和肿瘤免疫治疗的重要平台。然而,稳定性不足仍是制约mRNA疫苗广泛推广应用及产业化发展的关键瓶颈。mRNA分子本身易受物理、化学及生物因素影响而发生降解,而脂质纳米颗粒递送系统在储存、冻融及运输过程中则容易出现颗粒聚集、粒径增大、脂质膜结构改变及mRNA泄漏等问题,从而影响疫苗的免疫原性和安全性。本文围绕mRNA疫苗的稳定性,分析了mRNA降解、脂质纳米颗粒不稳定以及疫苗活性在生产、运输和储存过程中降低的潜在机制,并从分子结构、序列优化、化学修饰、递送系统、生产工艺以及储存条件等方面总结了影响其物理、化学和功能稳定性的关键因素。通过综述提高mRNA疫苗稳定性的最新进展,包括合理的mRNA工程设计、递送平台优化、新型稳定化辅料的开发,以及生产和保存技术的改进,以期为mRNA疫苗的长期稳定性研究与产业化开发提供新的思路。

    Abstract:

    As an emerging nucleic acid vaccine technology, mRNA vaccines have undergone rapid development and achieved commercial application since the COVID-19 pandemic. Owing to their flexible design, short development cycles, and ability to induce both humoral and cellular immune responses, this technology has become an important platform for infectious disease prevention and control as well as cancer immunotherapy. However, insufficient stability remains a critical bottleneck hindering the widespread application and industrial development of mRNA vaccines. The mRNA molecule itself is susceptible to degradation due to physical, chemical, and biological factors, while the lipid nanoparticle delivery system is prone to issues such as particle aggregation, increased particle size, structural changes in the lipid membrane, and mRNA leakage during storage, freeze-thaw cycles, and transportation, thereby compromising the immunogenicity and safety of the vaccine. This review focuses on the stability of mRNA vaccines, analyzing the potential mechanisms of mRNA degradation, lipid nanoparticle instability, and the decrease in vaccine activity during production, transportation, and storage, and summarizing the key factors affecting their physical, chemical, and functional stability from the perspectives of molecular structure, sequence optimization, chemical modification, delivery systems, manufacturing processes, and storage conditions. By reviewing the latest advances in improving mRNA vaccine stability, including rational mRNA engineering design, optimization of delivery platforms, development of novel stabilizing excipients, and improvements in manufacturing and preservation technologies, this review aims to provide new insights for the long-term stability research and industrial development of mRNA vaccines.

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万加武,周明,傅振芳,刘爵,赵凌. mRNA疫苗稳定性研究进展与挑战[J].华中农业大学学报,2026,45(4):174-188

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  • 收稿日期:2025-11-08
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  • 在线发布日期: 2026-08-11
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