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

IF 6.5 1区 医学 Q1 IMMUNOLOGY
Jing Wang, Kaixing Wu, Yu Liu, Shiyao Wang, Li Zhao, Donghui Zhang, Runhui Liu, Yuhong Ren, Shuai Shao, Qin Liu
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Abstract

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.

一种编码IHNV糖蛋白的mRNA疫苗的研制保护虹鳟免受感染。
mRNA疫苗已显示出在预防人类疾病和控制牲畜感染方面的巨大潜力。然而,mRNA疫苗在水产养殖中的应用,特别是在鱼类上的应用仍然有限。感染性造血坏死病毒(IHNV)是一种RNA病毒,主要影响虹鳟(Oncorhynchus mykiss),导致高死亡率。在这项研究中,我们系统地设计了三种utr优化的mRNA结构,表现出可比和持续的体外抗原表达。在包封后,mG1-LNP配方,结合内源性抗原特异性,提供了强大的相对保护,对抗IHNV的攻击,同时提高了IgM和中和抗体的水平。此外,剂量-反应分析确定10 μg/剂量为免疫优化方案,可激发有效的免疫原性。此外,生物分布分析显示,mG1-LNP在注射部位和肝脏组织中被28 dpv完全清除,证实了良好的生物安全性。总之,我们的工作证明了mRNA-LNP疫苗在虹鳟鱼中抗传染性IHNV的成功开发,提供了mRNA-LNP疫苗在水产养殖中的有效性的第一个实证证明。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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