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表达猪瘟病毒E2蛋白的gE/gI/TK基因缺失伪狂犬病病毒变异株在猪体内的安全性和免疫原性

Safety and immunogenicity of a gE/gI/TK gene-deleted pseudorabies virus variant expressing the E2 protein of classical swine fever virus in pigs.

作者信息

Lei Jian-Lin, Xia Shui-Li, Wang Yimin, Du Mingliang, Xiang Guang-Tao, Cong Xin, Luo Yuzi, Li Lian-Feng, Zhang Lingkai, Yu Jiahui, Hu Yonghao, Qiu Hua-Ji, Sun Yuan

机构信息

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China; College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

出版信息

Immunol Lett. 2016 Jun;174:63-71. doi: 10.1016/j.imlet.2016.04.014. Epub 2016 Apr 22.

DOI:10.1016/j.imlet.2016.04.014
PMID:27113530
Abstract

Classical swine fever (CSF) and pseudorabies (PR) are both major infectious diseases of pigs, causing enormous economic losses to the swine industry in many countries. A marker vaccine that enables differentiation of infected from vaccinated animals (DIVA) is highly desirable for control and eradication of these two diseases in endemic areas. Since late 2011, PR outbreaks have been frequently reported in many Bartha-K61-vaccinated pig farms in China. It has been demonstrated that a pseudorabies virus (PRV) variant with altered antigenicity and increased pathogenicity was responsible for the outbreaks. Previously, we showed that rPRVTJ-delgE/gI/TK, a gE/gI/TK-deleted PRV variant, was safe for susceptible animals and provided a complete protection against lethal PRV variant challenge, indicating that rPRVTJ-delgE/gI/TK can be used as an attractive vaccine vector. To develop a safe bivalent vaccine against CSF and PR, we generated a recombinant virus rPRVTJ-delgE/gI/TK-E2 expressing the E2 protein of classical swine fever virus (CSFV) based on rPRVTJ-delgE/gI/TK and evaluated its safety and immunogenicity in pigs. The results indicated that pigs (n=5) immunized with rPRVTJ-delgE/gI/TK-E2 of different doses did not exhibit clinical signs or viral shedding following immunization, the immunized pigs produced anti-PRV or anti-CSFV neutralizing antibodies and the pigs immunized with 10(6) or 10(5) TCID50 rPRVTJ-delgE/gI/TK-E2 were completely protected against the lethal challenge with either CSFV Shimen strain or variant PRV TJ strain. These findings suggest that rPRVTJ-delgE/gI/TK-E2 is a promising bivalent DIVA vaccine candidate against CSFV and PRV coinfections.

摘要

猪瘟(CSF)和伪狂犬病(PR)都是猪的主要传染病,给许多国家的养猪业造成了巨大的经济损失。在流行地区,一种能够区分感染动物和接种疫苗动物(DIVA)的标记疫苗对于控制和根除这两种疾病非常有必要。自2011年末以来,中国许多接种了Bartha-K61疫苗的猪场频繁报告发生PR疫情。已经证明,抗原性改变和致病性增加的伪狂犬病病毒(PRV)变种是疫情的罪魁祸首。此前,我们表明,rPRVTJ-delgE/gI/TK,一种缺失gE/gI/TK的PRV变种,对易感动物是安全的,并能提供完全保护以抵御致死性PRV变种的攻击,这表明rPRVTJ-delgE/gI/TK可作为一种有吸引力的疫苗载体。为了开发一种针对CSF和PR的安全二价疫苗,我们基于rPRVTJ-delgE/gI/TK构建了一种表达猪瘟病毒(CSFV)E2蛋白的重组病毒rPRVTJ-delgE/gI/TK-E2,并在猪身上评估了其安全性和免疫原性。结果表明,用不同剂量的rPRVTJ-delgE/gI/TK-E2免疫的猪(n = 5)在免疫后未表现出临床症状或病毒脱落,免疫猪产生了抗PRV或抗CSFV中和抗体,并且用10(6)或10(5) TCID50 rPRVTJ-delgE/gI/TK-E2免疫的猪完全受到保护,免受CSFV石门株或变异PRV TJ株的致死性攻击。这些发现表明,rPRVTJ-delgE/gI/TK-E2是一种有前景的针对CSFV和PRV混合感染的二价DIVA疫苗候选物。

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