Kisakov Denis N, Karpenko Larisa I, Kisakova Lyubov A, Sharabrin Sergey V, Borgoyakova Mariya B, Starostina Ekaterina V, Taranov Oleg S, Ivleva Elena K, Pyankov Oleg V, Zaykovskaya Anna V, Dmitrienko Elena V, Yakovlev Vladimir A, Tigeeva Elena V, Bauer Irina Alekseevna, Krasnikova Svetlana I, Rudometova Nadezhda B, Rudometov Andrey P, Sergeev Artemiy A, Ilyichev Alexander A
State Research Center of Virology and Biotechnology "Vector", Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, Russia.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Vaccines (Basel). 2025 Jan 13;13(1):65. doi: 10.3390/vaccines13010065.
Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution. In the first part of the study, the optimal conditions providing low traumatization and high expression of the model mRNA-GFP molecule in the tissues of laboratory animals were determined. Then, we used the selected protocol to immunize BALB/c mice with mRNA-RBD encoding the SARS-CoV-2 receptor-binding domain (RBD). It was demonstrated that mice vaccinated with naked mRNA-RBD developed a high level of specific antibodies with virus-neutralizing activity. The vaccine also induced a strong RBD-specific T-cell response and reduced the viral load in the lungs of the animals after infection with the SARS-CoV-2 virus. The level of immune response in mice immunized with mRNA-RBD using a spring-loaded jet injector was comparable to that in animals immunized with mRNA-RBD encapsulated in LNPs. In this study, the efficacy of an inexpensive, simple, and safe method of mRNA delivery using a spring-loaded jet injector was evaluated and validated. Our findings suggest that the jet injection method may be a possible alternative to LNPs for delivering mRNA vaccines against SARS-CoV-2 infection.
尽管包裹在脂质纳米颗粒（LNP）中的mRNA疫苗在临床试验中已显示出安全性，严重不良事件极少，但仍有进一步降低mRNA反应原性的机会。裸mRNA疫苗的开发可能会提高疫苗耐受性。使用喷射注射法进行裸核酸递送可能是一种解决方案。在研究的第一部分，确定了在实验动物组织中提供低创伤和模型mRNA-GFP分子高表达的最佳条件。然后，我们使用选定的方案用编码严重急性呼吸综合征冠状病毒2（SARS-CoV-2）受体结合域（RBD）的mRNA-RBD免疫BALB/c小鼠。结果表明，用裸mRNA-RBD疫苗接种的小鼠产生了高水平的具有病毒中和活性的特异性抗体。该疫苗还诱导了强烈的RBD特异性T细胞反应，并降低了感染SARS-CoV-2病毒后动物肺部的病毒载量。使用弹簧加载喷射注射器用mRNA-RBD免疫的小鼠的免疫反应水平与用包裹在LNP中的mRNA-RBD免疫的动物相当。在本研究中，评估并验证了使用弹簧加载喷射注射器进行mRNA递送的一种廉价、简单且安全的方法的有效性。我们的研究结果表明，喷射注射法可能是替代LNP用于递送抗SARS-CoV-2感染mRNA疫苗的一种可行方法。
