Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge
Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge
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DOI：
10.1016/j.vaccine.2015.09.066
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发表时间：
2015-10-26
期刊：
影响因子：
5.5
通讯作者：
Liu, Zheng-Fei
中科院分区：
文献类型：
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作者：
Hu, Rui-Ming;Zhou, Qing;Liu, Zheng-Fei
新出现的中国伪狂犬病病毒（PRV）变异体的一个显著特征是，它能够在接种Bartha-K61疫苗的猪场中引起生长猪的严重神经系统症状和高死亡率。已经开发了单基因或多基因缺失的活疫苗候选物;然而，没有一种在生长猪中进行了彻底评价。在这里，我们产生了rSMX Delta gI/gE Delta TK，一种TK、gI和gE基因缺陷的减毒PRV变体。减毒病毒的生长动力学与野生型（wt）毒株相似。对1日龄仔猪安全。用10（6.0）TCID 50 rSMX Delta gI/gE Delta TK或一剂市售Bartha-K61疫苗或DMEM肌内免疫20头1日龄断奶仔猪，并在接种后28天用10（7.0）TCID 50 wt病毒鼻内攻毒。rSMX Delta gI/gE Delta TK疫苗对PRV变异株SMX和Bartha-K61株均能产生较高水平的中和抗体，而Bartha-K61疫苗对SMX的中和抗体活性较低。攻毒后，rSMX Delta gI/gE Delta TK组所有猪均存活，无任何临床体征，而未接种组显示100%死亡率，Bartha-K61组显示重度呼吸道症状，5头猪中有3头显示重度神经系统体征。与Bartha-K61组相比，rSMX Delta gI/gE Delta TK组的猪体重显著增加，病毒排泄滴度和时间显著减少。此外，还在绵羊中评价了rSMX Delta gI/gE Delta TK的安全性和有效性，并在生长猪中与当地疫苗进行了比较。这些数据表明，减毒株rSMX Delta gI/gE Delta TK是一种有希望的活标记疫苗候选物，可用于在出现PRV变异体的情况下进行PR控制。(C)2015爱思唯尔有限公司版权所有。
One of the distinct features of the emerging Chinese pseudorabies virus (PRV) variant is its ability to cause severe neurological signs and high mortality in growing pigs in Bartha-K61-vaccinated pig farms. Either single- or multiple-gene-deleted live vaccine candidates have been developed; however, none was evaluated thoroughly in growing pigs. Here, we generated rSMX Delta gI/gE Delta TK, an attenuated PRV variant with defects in TK, gI and gE genes. The growth kinetics of the attenuated virus was similar to the wild type (wt) strain. It was safe for 1-day-old piglets. Twenty one-day-old weaned pigs were immunized intramuscularly either with 10(6.0) TCID50 of rSMX Delta gI/gE Delta TK or one dose of commercial Bartha-K61 vaccine, or with DMEM, and were challenged intranasally with 10(7.0) TCID50 wt virus at 28 days post vaccination. rSMX Delta gI/gE Delta TK elicited higher level neutralization antibody against both PRV variant SMX and Bartha-K61 strain, while Bartha-K61 vaccine elicited lower neutralization activity of antibody against SMX. After challenge, all pigs in rSMX Delta gI/gE Delta TK group survived without any clinical signs, while unvaccinated group showed 100% mortality, and Bartha-K61 group showed severe respiratory symptoms and 3 out of 5 pigs exhibited severe neurological signs. Pigs in rSMX Delta gI/gE Delta TK group gained significantly higher body weight and diminished viral excretion titer and period, compared with Bartha-K61 group. Furthermore, the safety and efficacy of rSMX Delta gI/gE Delta TK was also evaluated in sheep and compared with local vaccine in growing pigs. These data suggest that the attenuated strain rSMX Delta gI/gE Delta TK is a promising live marker vaccine candidate for PR control in the context of emerging PRV variants. (C) 2015 Elsevier Ltd. All rights reserved.