基于鸭肠炎病毒的减毒活疫苗对1型和3型鸭甲型肝炎病毒的作用

Live Attenuated Vaccine Based on Duck Enteritis Virus against Duck Hepatitis A Virus Types 1 and 3.

作者信息

Zou Zhong, Ma Ji, Huang Kun, Chen Huanchun, Liu Ziduo, Jin Meilin

机构信息

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, China; College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of AgricultureWuhan, China.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityWuhan, China; College of Veterinary Medicine, Huazhong Agricultural UniversityWuhan, China.

出版信息

Front Microbiol. 2016 Oct 10;7:1613. doi: 10.3389/fmicb.2016.01613. eCollection 2016.

Abstract

As causative agents of duck viral hepatitis, duck hepatitis A virus type 1 (DHAV-1) and type 3 (DHAV-3) causes significant economic losses in the duck industry. However, a licensed commercial vaccine that simultaneously controls both pathogens is currently unavailable. Here, we generated duck enteritis virus recombinants (rC-KCE-2VP1) containing both VP1 from DHAV-1 (VP1/DHAV-1) and VP1 from DHAV-3 (VP1/DHAV-3) between UL27 and UL26. A self-cleaving 2A-element of FMDV was inserted between the two different types of VP1, allowing production of both proteins from a single open reading frame. Immunofluorescence and Western blot analysis results demonstrated that both VP1 proteins were robustly expressed in rC-KCE-2VP1-infected chicken embryo fibroblasts. Ducks that received a single dose of rC-KCE-2VP1 showed potent humoral and cellular immune responses and were completely protected against challenges of both pathogenic DHAV-1 and DHAV-3 strains. The protection was rapid, achieved as early as 3 days after vaccination. Moreover, viral replication was fully blocked in vaccinated ducks as early as 1 week post-vaccination. These results demonstrated, for the first time, that recombinant rC-KCE-2VP1 is potential fast-acting vaccine against DHAV-1 and DHAV-3.

摘要

作为鸭病毒性肝炎的病原体,1型鸭甲型肝炎病毒(DHAV-1)和3型鸭甲型肝炎病毒(DHAV-3)给养鸭业造成了巨大的经济损失。然而,目前尚无同时控制这两种病原体的许可商业疫苗。在此,我们构建了鸭肠炎病毒重组体(rC-KCE-2VP1),其在UL27和UL26之间同时包含来自DHAV-1的VP1(VP1/DHAV-1)和来自DHAV-3的VP1(VP1/DHAV-3)。在两种不同类型的VP1之间插入了口蹄疫病毒的自切割2A元件,使得能够从单个开放阅读框产生两种蛋白质。免疫荧光和蛋白质印迹分析结果表明,两种VP1蛋白在rC-KCE-2VP1感染的鸡胚成纤维细胞中均能高效表达。接受单剂量rC-KCE-2VP1的鸭表现出强烈的体液免疫和细胞免疫反应,并对致病性DHAV-1和DHAV-3毒株的攻击具有完全的保护作用。这种保护作用迅速,在接种疫苗后3天就可实现。此外,在接种疫苗后1周,接种疫苗的鸭体内的病毒复制就被完全阻断。这些结果首次证明,重组体rC-KCE-2VP1是一种针对DHAV-1和DHAV-3的潜在快速起效疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ee/5056193/bac48cbf3668/fmicb-07-01613-g001.jpg

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