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由HA-TM/HA-TM和M1组成的H5N6病毒样颗粒在番鸭中的生物学特性和免疫学特性

Biological characteristics and immunological properties in Muscovy ducks of H5N6 virus-like particles composed of HA-TM/HA-TM and M1.

作者信息

Qin Jianru, Zhang Yun, Shen Xiaoting, Gong Lang, Xue Chunyi, Cao Yongchang

机构信息

a State Key Laboratory of Biocontrol , Life Sciences School, Sun Yat-sen University , Guangzhou , People's Republic of China.

出版信息

Avian Pathol. 2019 Feb;48(1):35-44. doi: 10.1080/03079457.2018.1546375. Epub 2018 Nov 26.

Abstract

Highly pathogenic avian influenza viruses (HPAIVs), including H5N6 strains, pose threats to the health of humans and poultry. Waterfowl play a crucial role as a reservoir of HPAIVs. Since current influenza vaccines induce poor antibody titres in waterfowl, there is an urgent need to develop an efficient vaccine against H5N6 infection. In this study, we constructed two H5N6 virus-like particles (VLPs) composed of matrix-1 (M1) and haemagglutinin of wildtype (HA-TM) or haemagglutinin with transmembrane domain replacement (HA-TM) (designated as H5N6 VLPs-TM and H5N6 VLPs-TM). Biological characteristics of the composed H5N6 VLPs were compared including localization, expression, contents of HA trimers, thermal stability, morphology and immunogenicity in Muscovy ducks. Our results indicate that the H5N6 VLPs-TM contained more HA trimers and presented better thermal stability. Moreover, Muscovy ducks immunized with H5N6 VLPs-TM produced higher titres of HI antibody and IFN-γ compared with those immunized with the same dose of H5N6 VLP-TM, thus providing a promising approach for the development of influenza virus vaccines for waterfowl. RESEARCH HIGHLIGHTS H5N6 VLPs-TM had more HA trimers and resisted higher temperature than H5N6 VLPs-TM H5N6 VLPs-TM induced higher titre of HI than H5N6 VLPs-TM in Muscovy ducks.

摘要

高致病性禽流感病毒(HPAIVs),包括H5N6毒株,对人类和家禽的健康构成威胁。水禽作为HPAIVs的储存宿主发挥着关键作用。由于目前的流感疫苗在水禽中诱导产生的抗体滴度较低,因此迫切需要开发一种针对H5N6感染的高效疫苗。在本研究中,我们构建了两种由基质蛋白-1(M1)和野生型血凝素(HA-TM)或跨膜结构域替换的血凝素(HA-TM)组成的H5N6病毒样颗粒(VLPs)(分别命名为H5N6 VLPs-TM和H5N6 VLPs-TM)。比较了所构建的H5N6 VLPs的生物学特性,包括在番鸭中的定位、表达、HA三聚体含量、热稳定性、形态和免疫原性。我们的结果表明,H5N6 VLPs-TM含有更多的HA三聚体,并且具有更好的热稳定性。此外,与用相同剂量的H5N6 VLP-TM免疫的番鸭相比,用H5N6 VLPs-TM免疫的番鸭产生了更高滴度的HI抗体和IFN-γ,从而为开发水禽流感病毒疫苗提供了一种有前景的方法。研究亮点:H5N6 VLPs-TM比H5N6 VLPs-TM含有更多的HA三聚体,并且能抵抗更高的温度;在番鸭中,H5N6 VLPs-TM诱导产生的HI滴度比H5N6 VLPs-TM更高。

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