A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks
A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks
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DOI：
10.1128/jvi.05420-11
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Chen, Hualan
中科院分区：
文献类型：
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作者：
Liu, Jinxiong;Chen, Pucheng;Chen, Hualan
鸭在维持高致病性H5N1禽流感病毒（aiv）的自然界中发挥着重要作用，成功控制鸭的aiv对根除家禽疾病和预防人类疾病具有重要意义。灭活流感疫苗价格昂贵，劳动密集型，通常需要2至3周才能在鸭中诱导保护性免疫。在许多产鸭地区，常规使用减毒鸭肠炎病毒（DEV；一种疱疹病毒）疫苗来控制致命的DEV感染。在这里，我们首先建立了一个系统，通过转染重叠的fosmid dna来产生DEV疫苗株。利用该系统构建了两种重组病毒rDEV-ul41HA和rDEV-us78HA，将H5N1病毒A/duck/Anhui/1/06的血凝素（HA）基因插入到病毒基因组ul41基因内或us7和us8基因之间，并稳定地维持了HA基因的表达。鸭实验表明，rDEV-us78HA对DEV致死性攻毒具有与DEV活疫苗相似的保护作用；重要的是，单剂量10(6)PFU的rDEV-us78HA在疫苗接种后短短3天内就对致命的H5N1病毒攻击产生了完全保护。接种rDEV-ul41HA对鸭的杀伤作用略弱于接种rDEV-us78HA。这些结果首次表明，重组DEV适于作为二价减毒活疫苗，对鸭的DEV和H5N1病毒感染提供快速保护。
Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 10(6) PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks.