mRNA疫苗稳定性研究进展与挑战
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1.华中农业大学动物医学院;2.扬州大学兽医学院

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


Advances and challenges in the stability of mRNA vaccines
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National Natural Science Foundation of China Joint Funds (U24A20449); National Natural Science Foundation of China Key Program (32430105)

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    摘要:

    mRNA疫苗作为新兴的核酸疫苗技术,自新冠疫情以来实现了快速发展与商业化应用。该技术具有设计灵活、研发周期短以及能够同时诱导体液免疫与细胞免疫等优势,已成为传染病防控与肿瘤免疫治疗的重要疫苗平台。然而,稳定性不足仍是制约mRNA疫苗广泛推广与产业化发展的关键问题。mRNA分子本身易受物理、化学及生物学因素影响而降解,而其脂质纳米颗粒递送系统在储存、冻融及运输过程中亦易发生颗粒聚集、粒径增大、膜结构破坏及mRNA泄漏等问题,从而削弱疫苗的免疫原性与安全性。本文围绕mRNA疫苗的稳定性问题,从分子结构、递送系统、生产工艺与储存条件等多个方面展开综述,重点分析影响其物理、化学及功能稳定性的关键因素,并对未来提升稳定性的策略方向进行展望,旨在为mRNA疫苗的长期稳定性研究与产业化开发提供研究思路。

    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 comprehensively addresses the stability challenges of mRNA vaccines, examining key factors affecting their physical, chemical, and functional stability from multiple perspectives, including molecular structure, delivery systems, production processes, and storage conditions. Furthermore, it outlines future strategies for enhancing stability, with the aim of providing research insights for long-term stability studies and industrial development of mRNA vaccines.

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  • 收稿日期:2025-10-19
  • 最后修改日期:2026-04-06
  • 录用日期:2026-04-06
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