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Avian adenovirus CELO recombinants expressing VP2 of infectious bursal disease virus induce protection against bursal disease in chickens

机译:表达传染性法氏囊病病毒VP2的禽腺病毒CELO重组体可预防鸡的法氏囊病

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摘要

To develop a CELO virus vector that can induce protection against infectious bursal disease, CELO viruses expressing the host-protective antigen VP2 of infectious bursal disease virus (IBDV) were constructed. In the engineered recombinants, the VP2 gene (the 441-first codons of the IBDA polyprotein) was placed under the control of the CMV promoter. Two positions in the CELO genome were chosen to insert the VP2 expression cassette. The recombinants were found apathogenic, when inoculated by different routes and even at high doses (up to to, per animal). Chickens vaccinated oro-nasally with these different recombinants and challenged with very virulent IBDV were found to be poorly protected. In contrast, when inoculated with one or two (subcutaneous or intradermic) injections of CELOa-VP2, the chickens showed no clinical signs and no mortality after challenge. In the vaccinated chickens, the titers of neutralization antibody reached 7-9 values, showing that protection Could be explained by the induction of a sufficient humoral response. After challenge, the weight ratio Bursa of Fabricius/body was about 2.5parts per thousand, a value similar to that obtained with the commercial Bur706 vaccine. However, histological lesions in the Bursa of Fabricius were observed, showing that a complete protection was not totally achieved. Contact transmission was evidenced. Protection was also obtained when inoculation of CELOa-VP2 was carried out in ovo. Prime-boost strategies were also tested with the CELOa-VP2 vector used in association with the purified VP2 antigen, or DNA encoding VP2 or a CELO vector expressing chicken myeloid growth factor (cMGF). None of these regimens were shown to substantially increase the level of protection when compared to double CELOa-VP2 inoculations. These results indicate that CELO-based vectors are useful to safely induce a strong protective immunity against vvIBDV in chickens.
机译:为了开发可诱导针对传染性法氏囊病的保护的CELO病毒载体,构建了表达传染性法氏囊病病毒(IBDV)的宿主保护性抗原VP2的CELO病毒。在工程重组体中,将VP2基因(IBDA多蛋白的441位密码子)置于CMV启动子的控制下。选择CELO基因组中的两个位置以插入VP2表达盒。当通过不同途径甚至以高剂量(最多每只动物)接种时,发现重组体无致病性。发现用这些不同重组体经鼻鼻腔接种疫苗并用强力IBDV攻击的鸡的保护性较差。相反,当接种一或两次(皮下或皮下注射)CELOa-VP2疫苗时,鸡在攻击后没有临床症状,也没有死亡率。在接种疫苗的鸡中,中和抗体的滴度达到7-9值,表明保护作用可以通过诱导足够的体液反应来解释。攻击后,Fabricius /身体的Bursa重量比约为2.5千分之几,该值与商业Bur706疫苗获得的值相似。然而,观察到法布里第乌斯氏囊的组织学损伤,表明不能完全实现完整的保护。证明了接触传播。当在卵内进行CELOa-VP2的接种时,也获得了保护。还使用与纯化的VP2抗原结合使用的CELOa-VP2载体或编码VP2的DNA或表达鸡髓样生长因子(cMGF)的CELO载体测试了初免-加强策略。与双重CELOa-VP2接种相比,这些方案均未显示可显着提高保护水平。这些结果表明,基于CELO的载体可用于安全诱导鸡中针对vvIBDV的强保护性免疫。

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