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<p>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 (<i>Oncorhynchus mykiss</i>), 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.</p>

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Development of an mRNA vaccine encoding IHNV glycoprotein protects rainbow trout (Oncorhynchus mykiss) from infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月22日

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  • Jing Wang,
  • Kaixin Wu,
  • Yu Liu,
  • Shiyao Wang,
  • Li Zhao,
  • Donghui Zhang,
  • Runhui Liu,
  • Yuhong Ren,
  • Shuai Shao,
  • Qin Liu

摘要

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.