Lu Yihan, Qian Ciying, Huang Yang, Ren Tianyu, Xie Wuzhi, Xia Ningshao, Li Shaowei
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Discipline of Intelligent Instrument and Equipment, Department of Experimental Medicine, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China.
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Discipline of Intelligent Instrument and Equipment, Department of Experimental Medicine, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen, China.
Int J Biol Macromol. 2025 Jun 24;319(Pt 3):145501. doi: 10.1016/j.ijbiomac.2025.145501.
The COVID-19 pandemic has highlighted the transformative potential of messenger RNA (mRNA) vaccines in biomedicine, thanks to their rapid design, scalable production, and strong immunogenicity. Nonetheless, their widespread adoption remains hindered by challenges related to sequence optimization, delivery efficiency, thermostability, and safety. This review systematically summarizes recent progress in mRNA vaccine development, including advances in molecular engineering, delivery platforms, adjuvant properties, and artificial intelligence (AI)-driven predictive modeling. It covers codon optimization, nucleoside modification, untranslated region (UTR) engineering, and novel structural formats such as self-amplifying and circular mRNAs. The review also compares various delivery systems-including lipid nanoparticles, cationic polymers, and virus-like particles-focusing on their physicochemical characteristics and translational applicability. Particular attention is given to the intrinsic adjuvant properties of mRNA molecules and their delivery vehicles, as well as strategies for incorporating exogenous adjuvants to modulate immune responses. Furthermore, the article provides a succinct overview of key preclinical and clinical advancements in mRNA vaccines targeting major infectious diseases (e.g., HIV, influenza, RSV, rabies) and tumor-associated antigens (e.g., HPV). This review is among the first to highlight breakthroughs in the application of AI for antigen screening, mRNA sequence optimization, lipid component selection, and vaccine stability prediction. Finally, the review addresses current platform limitations and proposes future directions for interdisciplinary collaboration, offering both theoretical insights and practical recommendations for the safe and effective implementation of next-generation mRNA vaccines.
2019冠状病毒病（COVID-19）大流行凸显了信使核糖核酸（mRNA）疫苗在生物医学中的变革潜力，这得益于其快速设计、可扩展生产以及强大的免疫原性。尽管如此，与序列优化、递送效率、热稳定性和安全性相关的挑战仍然阻碍着它们的广泛应用。本综述系统地总结了mRNA疫苗开发的最新进展，包括分子工程、递送平台、佐剂特性以及人工智能（AI）驱动的预测建模等方面的进展。它涵盖了密码子优化、核苷修饰、非翻译区（UTR）工程以及自我扩增和环状mRNA等新型结构形式。该综述还比较了各种递送系统，包括脂质纳米颗粒、阳离子聚合物和病毒样颗粒，重点关注它们的物理化学特性和转化适用性。特别关注mRNA分子及其递送载体的内在佐剂特性，以及纳入外源性佐剂以调节免疫反应的策略。此外，本文简要概述了针对主要传染病（如艾滋病毒、流感、呼吸道合胞病毒、狂犬病）和肿瘤相关抗原（如人乳头瘤病毒）的mRNA疫苗在临床前和临床方面的关键进展。本综述是最早强调人工智能在抗原筛选、mRNA序列优化、脂质成分选择和疫苗稳定性预测应用方面取得突破的综述之一。最后，该综述阐述了当前平台的局限性，并提出了跨学科合作的未来方向，为安全有效地实施下一代mRNA疫苗提供了理论见解和实际建议。
