Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China.
Biomacromolecules. 2024 Jul 8;25(7):4281-4291. doi: 10.1021/acs.biomac.4c00365. Epub 2024 Jun 6.
Messenger ribonucleic acid (mRNA) vaccines, serving as a rapid and easily scalable emergency preventive measure, have played a pivotal role in preventing infectious diseases. The effectiveness of mRNA vaccines heavily relies on the delivery carrier, but the current market options are predominantly lipid nanoparticles. Their intricate preparation process and high transportation costs pose challenges for widespread use in remote areas. In this study, we harnessed FDA-approved polymer PLGA and lipid components widely employed in clinical experiments to craft a ready-to-use mRNA vaccine delivery system known as lipid-polymer hybrid nanoparticles (LPP). Following formulation optimization, the PDCD nanoparticles emerged as the most effective, showcasing exceptional mRNA delivery capabilities both in vitro and in vivo. Loading PDCD nanoparticles with mRNA encoding the H1N1 influenza virus HA antigen-fused M2e peptide enabled the successful induction of M2e-specific antibodies and T cell immune responses in immunized mice. After three rounds of vaccine immunization, the mice demonstrated weight recovery to normal levels and maintained a survival rate exceeding 80% following an encounter with the H1N1 influenza virus. The innovative mRNA delivery system that we designed demonstrates outstanding effectiveness in preventing infectious diseases, with the potential to play an even more significant role in future clinical applications.
信使核糖核酸（mRNA）疫苗作为一种快速且易于扩展的紧急预防措施，在预防传染病方面发挥了关键作用。mRNA 疫苗的有效性在很大程度上依赖于递送载体，但目前市场上的选择主要是脂质纳米粒。它们复杂的制备过程和高昂的运输成本给在偏远地区的广泛应用带来了挑战。在这项研究中，我们利用了美国食品和药物管理局（FDA）批准的聚合物 PLGA 和广泛用于临床试验的脂质成分，开发了一种即用型的 mRNA 疫苗递送系统，称为脂质-聚合物混合纳米粒（LPP）。经过配方优化，PDCD 纳米粒是最有效的，在体外和体内都表现出了出色的 mRNA 递送能力。将 PDCD 纳米粒装载上编码甲型 H1N1 流感病毒 HA 抗原融合 M2e 肽的 mRNA，能够成功诱导免疫小鼠产生 M2e 特异性抗体和 T 细胞免疫反应。经过三轮疫苗免疫后，感染 H1N1 流感病毒的小鼠体重恢复到正常水平，存活率超过 80%。我们设计的创新 mRNA 递送系统在预防传染病方面表现出了卓越的效果，有望在未来的临床应用中发挥更重要的作用。
