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一种新型 H9 流感病毒 mRNA 疫苗可诱导针对感染的强大保护免疫。

A new H9 influenza virus mRNA vaccine elicits robust protective immunity against infection.

机构信息

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, People's Republic of China.

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, People's Republic of China.

出版信息

Vaccine. 2023 May 2;41(18):2905-2913. doi: 10.1016/j.vaccine.2023.03.049. Epub 2023 Mar 31.

DOI:10.1016/j.vaccine.2023.03.049
PMID:37005103
Abstract

Avian influenza virus (AIV) poses a great threat to the poultry industry and public health. However commercial vaccines only provide limited immunity due to rapid virus mutation and rearrangement. Here, we developed an mRNA-lipid nanoparticle (mRNA-LNP) vaccine expressing AIV immunogenic protein hemagglutinin (HA) and also assessed its safety and immune-protection efficacy in vivo. Specifically, its safety was tested by inoculation of SPF chicken embryos and chicks, and there showed no clinical manifestations and pathological changes in both. As for the immune efficacy, the antibody titers, IFN-γ production levels, and viral loads in various organs were analyzed. The results showed that chickens in the mRNA-LNP-inoculated groups produced higher specific antibody titers compared with that in the control group by hemagglutination inhibition (HI) test. Meanwhile, the ELISpot assay demonstrated that the expression of IFN-γ was markedly induced in the mRNA-LNP group, and the viral loads in multiple organs were decreased. In addition, HE shows no obvious pathomorphological changes in the lungs of the mRNA-LNP-inoculated group. While, there was severe inflammatory cell infiltration in the DMEM-treated group instead. Taken together, the vaccine prepared in this study was safe and could trigger potent cellular and humoral immune response to defend against virus infection.

摘要

禽流感病毒 (AIV) 对家禽业和公共卫生构成了巨大威胁。然而,由于病毒的快速突变和重排,商业疫苗只能提供有限的免疫力。在这里,我们开发了一种表达 AIV 免疫原性蛋白血凝素 (HA) 的 mRNA-脂质纳米颗粒 (mRNA-LNP) 疫苗,并评估了其在体内的安全性和免疫保护效果。具体来说,通过接种 SPF 鸡胚和雏鸡来测试其安全性,两者均未表现出临床症状和病理变化。至于免疫效果,分析了各种器官中的抗体滴度、IFN-γ 产生水平和病毒载量。结果表明,与对照组相比,mRNA-LNP 接种组的鸡通过血凝抑制 (HI) 试验产生了更高的特异性抗体滴度。同时,ELISpot 分析表明,mRNA-LNP 组 IFN-γ 的表达明显被诱导,并且多个器官中的病毒载量降低。此外,HE 显示 mRNA-LNP 接种组的肺部没有明显的病理形态变化,而 DMEM 处理组则有严重的炎症细胞浸润。总之,本研究制备的疫苗安全,并能引发强烈的细胞和体液免疫反应,抵御病毒感染。

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