Li Sha, Zheng Lu, Zhong Jingyi, Gao Xihui
Shanghai Pudong Hospital, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
Essays Biochem. 2025 May 1;69(2):EBC20253009. doi: 10.1042/EBC20253009.
Vaccination remains a cornerstone in preventing infectious diseases and managing outbreaks. The COVID-19 pandemic has underscored the revolutionary impact of mRNA vaccine technology, which utilizes pathogenderived genomic sequences to generate specific antigens. This process involves in vitro transcription of mRNA, encoding target antigens that are subsequently encapsulated within lipid nanoparticles (LNPs) for efficient delivery into host cells. Once internalized, the mRNA enables antigen expression, triggering a robust immune response. This platform dramatically accelerates vaccine development timelines and offers unparalleled adaptability, making mRNA vaccines particularly advantageous in addressing emerging infectious diseases. The clinical success of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) has fueled broader applications, including influenza, respiratory syncytial virus (RSV), Zika, and HIV. Notably, mRNA-1345 became the first FDA-approved RSV mRNA vaccine, while self-amplifying RNA and multivalent vaccines are advancing in trials. However, CureVac's CVnCoV failed due to lack of nucleoside modifications, and mRNA-1325 (Zika) showed poor immunogenicity. Additionally, mRNA-1365 (RSV) faced an FDA clinical hold due to safety concerns. These cases highlight the need for continued optimization in sequence design, delivery, and safety assessment. Despite advancements, a key hurdle persists, including mRNA instability, ultra-low storage requirements, and LNP liver accumulation. Innovations such as lyophilization and selective organ targeting technology are being explored to improve stability extrahepatic delivery. This review examines mRNA vaccine optimization strategies, clinical progress, and challenges, providing insights into future developments in this evolving field.
疫苗接种仍然是预防传染病和控制疫情的基石。新冠疫情凸显了mRNA疫苗技术的革命性影响,该技术利用病原体衍生的基因组序列来产生特定抗原。这一过程涉及mRNA的体外转录,编码靶抗原,随后将其封装在脂质纳米颗粒(LNP)中,以便有效地递送至宿主细胞。一旦被内化,mRNA就能实现抗原表达,触发强烈的免疫反应。这个平台极大地加快了疫苗研发的时间线,并提供了无与伦比的适应性,使得mRNA疫苗在应对新发传染病方面具有特别的优势。BNT162b2(辉瑞-生物科技公司)和mRNA-1273(莫德纳公司)的临床成功推动了更广泛的应用,包括流感、呼吸道合胞病毒(RSV)、寨卡病毒和艾滋病毒。值得注意的是,mRNA-1345成为首个获得美国食品药品监督管理局(FDA)批准的RSV mRNA疫苗,而自我扩增RNA和多价疫苗正在进行临床试验。然而,CureVac公司的CVnCoV因缺乏核苷修饰而失败,mRNA-1325(寨卡病毒)的免疫原性较差。此外,mRNA-1365(RSV)因安全问题面临FDA的临床搁置。这些案例凸显了在序列设计、递送和安全性评估方面持续优化的必要性。尽管取得了进展,但一个关键障碍仍然存在,包括mRNA的不稳定性、极低的储存要求以及LNP在肝脏中的积累。正在探索诸如冻干和选择性器官靶向技术等创新方法来提高稳定性和肝外递送。本综述探讨了mRNA疫苗的优化策略、临床进展和挑战,为这一不断发展领域的未来发展提供了见解。
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