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利用改进的酵母表面展示技术对传染性造血器官坏死病毒口服疫苗的初步研究。

Preliminary study of an oral vaccine against infectious hematopoietic necrosis virus using improved yeast surface display technology.

作者信息

Zhao Jing-Zhuang, Xu Li-Ming, Liu Miao, Cao Yong-Sheng, LaPatra Scott E, Yin Jia-Sheng, Liu Hong-Bai, Lu Tong-Yan

机构信息

Heilongjiang River Fishery Research Institute Chinese Academy of Fishery Sciences, Harbin 150070, PR China.

Clear Springs Foods Inc., Research Division, PO Box 712, Buhl, ID, USA.

出版信息

Mol Immunol. 2017 May;85:196-204. doi: 10.1016/j.molimm.2017.03.001. Epub 2017 Mar 8.

Abstract

Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease in the salmonid aquaculture industry. Because oral vaccines induce more efficient mucosal immunity than parenteral immunization, an oral vaccine was developed with an improved yeast cell surface display technology to induce an immune response to IHNV. The oral yeast vaccine, designated EBY100/pYD1-bi-G, was delivered orally to rainbow trout (Oncorhynchus mykiss) on days 1 and 32, and the nonspecific and specific immune responses were measured 50days after the first vaccination. In the hindgut, spleen, and head kidney, the expression of IFN-1 and Mx-1 was significantly upregulated after oral vaccination with EBY100/pYD1-bi-G, and the highest expression of IFN-1 and Mx-1 was observed in the spleen (7.5-fold higher than the control group) and head kidney (3.9-fold higher than the control group), respectively. Several markers of the adaptive immune response (IgM, IgT, CD4, and CD8) were also significantly upregulated, and the highest expression of these markers was observed in the hindgut, suggesting that the mucosal immune response was successfully induced by oral vaccination with EBY100/pYD1-bi-G. Sera from the orally vaccinated rainbow trout showed higher anti-IHNV neutralizing antibody titers (antibody titer 81±4) than the control sera (antibody titer 7±3), and the relative percentage survival after IHNV challenge was 45.8% compared with 2% in the control group. Although the protection afforded by this orally delivered vaccine was lower than that of a DNA vaccine (83%-98%), it is a promising candidate vaccine with which to protect larval fish against IHNV, which are most susceptible to the virus and difficult to inject with a DNA vaccine.

摘要

传染性造血器官坏死病毒(IHNV)是一种常见病原体,在鲑鱼养殖业中会引发严重疾病。由于口服疫苗比肠胃外免疫诱导产生的黏膜免疫更有效,因此利用改进的酵母细胞表面展示技术开发了一种口服疫苗,以诱导对IHNV的免疫反应。名为EBY100/pYD1-bi-G的口服酵母疫苗在第1天和第32天经口投喂给虹鳟(Oncorhynchus mykiss),并在首次接种疫苗50天后检测非特异性和特异性免疫反应。在用EBY100/pYD1-bi-G口服疫苗接种后,后肠、脾脏和头肾中IFN-1和Mx-1的表达显著上调,且在脾脏(比对照组高7.5倍)和头肾(比对照组高3.9倍)中分别观察到IFN-1和Mx-1的最高表达。适应性免疫反应的几个标志物(IgM、IgT、CD4和CD8)也显著上调,且在这些标志物的最高表达出现在后肠,这表明用EBY100/pYD1-bi-G口服疫苗成功诱导了黏膜免疫反应。口服接种疫苗的虹鳟血清显示出比对照血清更高的抗IHNV中和抗体滴度(抗体滴度81±4),对照血清的抗体滴度为7±3,且在IHNV攻毒后的相对存活率为45.8%,而对照组为2%。尽管这种口服疫苗提供的保护低于DNA疫苗(83%-98%),但它是一种有前景的候选疫苗,可用于保护最易感染该病毒且难以注射DNA疫苗的幼鱼免受IHNV侵害。

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