Yakovlev Vladimir A, Litvinova Victoria R, Rudometova Nadezhda B, Borgoyakova Mariya B, Tigeeva Elena V, Starostina Ekaterina V, Ivanova Ksenia I, Gudymo Andrei S, Danilchenko Natalia V, Perfilyeva Olga N, Makarova Kristina P, Vahitov Danil I, Zaitsev Boris N, Dmitrienko Elena V, Sharabrin Sergey V, Krasnikova Svetlana I, Kisakova Lyubov A, Kisakov Denis N, Ilyicheva Tatiana N, Marchenko Vasiliy Yu, Karpenko Larisa I, Rudometov Andrey P, Ilyichev Alexander A
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector», Rospotrebnadzor, 630559 Koltsovo, Russia.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Vaccines (Basel). 2025 Aug 21;13(8):883. doi: 10.3390/vaccines13080883.
The development of a vaccine against highly pathogenic avian influenza viruses subtype A/H5 is an urgent task due to concerns about its pandemic potential. In this study, we have developed an experimental mRNA vaccine, mRNA-H5, encoding a modified hemagglutinin trimer of influenza virus A/turkey/Stavropol/320-01/2020 (H5N8). BALB/c mice were immunized with the mRNA-H5 vaccine using lipid nanoparticles (LNPs) and needle-free jet injection (JI). Subsequently, the immune response to vaccine was assessed using ELISA, microneutralization assay, and ICS methods, and a challenge study was conducted. mRNA-H5 was shown to effectively stimulate specific humoral and T-cell immune responses. Moreover, mRNA-H5 delivered by LNPs and JI provided 100% protection of immunized mice against lethal challenge with homologous and heterologous strains of avian influenza virus (A/Astrakhan/3212/2020 (H5N8) and A/chicken/Magadan/14-7V/2022 (H5N1), respectively). The present results indicate that JI can be considered as an alternative to LNPs for mRNA delivery, and according to the literature, JI is safer than delivery using LNP. mRNA-H5 has potential as a vaccine against infection with highly pathogenic avian influenza A/H5 viruses with pandemic potential.
鉴于高致病性甲型流感病毒H5亚型具有大流行的可能性，开发针对该病毒的疫苗是一项紧迫任务。在本研究中，我们开发了一种实验性mRNA疫苗mRNA-H5，其编码甲型流感病毒A/火鸡/斯塔夫罗波尔/320-01/2020（H5N8）的修饰血凝素三聚体。使用脂质纳米颗粒（LNP）和无针喷射注射（JI）对BALB/c小鼠接种mRNA-H5疫苗。随后，使用酶联免疫吸附测定（ELISA）、微量中和试验和细胞内细胞因子染色（ICS）方法评估对疫苗的免疫反应，并进行了攻毒研究。结果表明，mRNA-H5能有效刺激特异性体液免疫和T细胞免疫反应。此外，通过LNP和JI递送的mRNA-H5分别为免疫小鼠提供了100%的保护，使其免受同源和异源禽流感病毒株（分别为A/阿斯特拉罕/3212/2020（H5N8）和A/鸡/马加丹/14-7V/2022（H5N1））的致死性攻击。目前的结果表明，JI可被视为用于mRNA递送的LNP的替代方法，并且根据文献，JI比使用LNP递送更安全。mRNA-H5有潜力作为一种疫苗，用于预防具有大流行可能性的高致病性甲型H5禽流感病毒感染。
