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评估一种含有自行设计的 CpG 序列的 DNA 疫苗对虹鳟(Oncorhynchus mykiss)J 基因型 IHNV 感染的作用。

Evaluation of a DNA vaccine with self-designed CpG sequences against J genotype IHNV infection in rainbow trout (Oncorhynchus mykiss).

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.

出版信息

Fish Shellfish Immunol. 2024 Nov;154:109942. doi: 10.1016/j.fsi.2024.109942. Epub 2024 Oct 5.

DOI:10.1016/j.fsi.2024.109942
PMID:39370023
Abstract

Rainbow trout suffer from infectious hematopoietic necrosis virus (IHNV) outbreaks, which lead to massive mortality and huge economic loss worldwide. The approved commercial vaccine is used for the prevention of IHN in Canada. Given that Chinese domestic J-genotype isolates are different from North American IHNV isolates, the development of an effective DNA vaccine against Chinese J-genotype isolates is urgent. In this study, we developed a DNA vaccine encoding glycoprotein based on our previously isolated IHNV GS21 strain and self-designed CpG sequences were supplemented as molecular adjuvants. The vaccinated rainbow trout were significantly protected against IHNV with approximately a relative percent survival (RPS) of 94.74 % compared to the unvaccinated group. Moreover, the specific antibody of IgM and neutralizing antibody (NAb) was significantly provoked after the vaccination. Particularly, the antiviral immune response was rapidly evoked in the early stage of vaccination including the up-regulation of Mx-1, IFN-Ⅰ, and IFN-γ. The IHNV load in vaccinated fish was apparently lower than that in the unvaccinated group. Furthermore, the integration of exogenous genes into the host chromosome and the spread of antimicrobial-resistant genes were not found. These results suggested that our vaccine enhances robust immune responses and evokes considerable protection against IHNV with limited genetically modified risk, which is an effective and promising vaccine candidate for further prevention of IHNV outbreaks.

摘要

虹鳟鱼易患传染性造血器官坏死病毒 (IHNV) 暴发,导致全球大量死亡和巨大的经济损失。加拿大批准的商业疫苗用于预防 IHNV。鉴于中国国内 J 基因型分离株与北美的 IHNV 分离株不同,因此迫切需要开发针对中国 J 基因型分离株的有效 DNA 疫苗。在这项研究中,我们基于先前分离的 IHNV GS21 株开发了一种编码糖蛋白的 DNA 疫苗,并补充了我们自行设计的 CpG 序列作为分子佐剂。与未接种疫苗的组相比,接种疫苗的虹鳟鱼对 IHNV 的保护率显著提高,约为 94.74%。此外,接种后 IgM 和中和抗体 (NAb) 的特异性抗体明显增加。特别是,抗病毒免疫反应在接种的早期阶段迅速被激发,包括 Mx-1、IFN-Ⅰ和 IFN-γ的上调。接种鱼体内的 IHNV 载量明显低于未接种组。此外,未发现外源基因整合到宿主染色体中和抗微生物耐药基因的传播。这些结果表明,我们的疫苗增强了强烈的免疫反应,并对 IHNV 产生了相当大的保护作用,遗传修饰风险有限,是进一步预防 IHNV 暴发的有效和有前途的候选疫苗。

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