Wang Jing, Wu Kaixing, Liu Yu, Wang Shiyao, Zhao Li, Zhang Donghui, Liu Runhui, Ren Yuhong, Shao Shuai, Liu Qin
State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, East China University of Science and Technology, Shanghai, China.
Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China.
NPJ Vaccines. 2025 Jul 22;10(1):162. doi: 10.1038/s41541-025-01222-w.
mRNA vaccines have demonstrated significant potential in preventing human diseases and controlling livestock infections. However, the application of mRNA vaccines in aquaculture, especially on fish, remains limited. Infectious hematopoietic necrosis virus (IHNV) is an RNA virus that mainly affects rainbow trout (Oncorhynchus mykiss), leading to high mortality rates. In this study, we systematically engineered three UTR-optimized mRNA constructs, exhibiting comparable and sustained in vitro antigen expression. Following encapsulation, the mG1-LNP formulation, incorporating endogenous antigen-specifics, conferred robust relative protection against IHNV challenge, accompanied by enhanced levels of IgM and neutralizing antibodies. Furthermore, dose-response profiling identified 10 μg/dose as the immunologically optimized regimen, eliciting efficient immunogenicity. Moreover, biodistribution analyses revealed complete mG1-LNP clearance from injection sites and hepatic tissues by 28 dpv, confirming favorable biosafety. Collectively, our work demonstrates the successful development of mRNA-LNP vaccine against infectious IHNV in rainbow trout, providing the first empirical demonstration of mRNA-LNP vaccine efficacy in aquaculture.
信使核糖核酸（mRNA）疫苗在预防人类疾病和控制家畜感染方面已显示出巨大潜力。然而，mRNA疫苗在水产养殖中的应用，尤其是在鱼类上的应用仍然有限。传染性造血坏死病毒（IHNV）是一种RNA病毒，主要影响虹鳟鱼（Oncorhynchus mykiss），导致高死亡率。在本研究中，我们系统地构建了三种经非翻译区（UTR）优化的mRNA构建体，它们在体外表现出相当且持续的抗原表达。包封后，包含内源性抗原特异性的mG1-LNP制剂对IHNV攻击具有强大的相对保护作用，同时伴有IgM和中和抗体水平的提高。此外，剂量反应分析确定10μg/剂量为免疫优化方案，可引发有效的免疫原性。此外，生物分布分析显示，到接种后28天，注射部位和肝脏组织中的mG1-LNP已完全清除，证实了良好的生物安全性。总体而言，我们的工作证明了针对虹鳟鱼传染性IHNV的mRNA-LNP疫苗的成功研发，为mRNA-LNP疫苗在水产养殖中的功效提供了首个实证。
