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表达传染性法氏囊病病毒VP2的禽腺病毒CELO重组体可诱导鸡对法氏囊病产生保护作用。

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

作者信息

Francois Achille, Chevalier Christophe, Delmas Bernard, Eterradossi Nicolas, Toquin Didier, Rivallan Gaëlle, Langlois Patrick

机构信息

Agence Française de Sécurité Sanitaire des Aliments, Molecular Biology Unit, Zoopôle Les Croix, B.P. 53, Ploufragan 22440, France.

出版信息

Vaccine. 2004 Jun 2;22(17-18):2351-60. doi: 10.1016/j.vaccine.2003.10.039.

Abstract

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 10(8) 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 2.5 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.

摘要

为开发一种能诱导针对传染性法氏囊病产生保护作用的CELO病毒载体,构建了表达传染性法氏囊病病毒(IBDV)宿主保护性抗原VP2的CELO病毒。在工程重组体中,VP2基因(IBDV多聚蛋白的第441个起始密码子)置于巨细胞病毒(CMV)启动子的控制之下。选择CELO基因组中的两个位置插入VP2表达盒。当通过不同途径甚至高剂量(每只动物高达10⁸)接种时,发现这些重组体无致病性。用这些不同的重组体经口鼻接种疫苗并受到超强毒力IBDV攻击的鸡,发现保护效果不佳。相反,当用CELOa-VP2进行一次或两次(皮下或皮内)注射接种时,鸡在受到攻击后未表现出临床症状且无死亡。在接种疫苗的鸡中,中和抗体滴度达到7 - 9,表明保护作用可通过诱导充分的体液反应来解释。受到攻击后,法氏囊与体重的比值约为千分之2.5,这一数值与使用商业Bur706疫苗所获得的数值相似。然而,在法氏囊中观察到了组织学损伤,表明并未完全实现完全保护。证实了接触传播。在鸡胚中接种CELOa-VP2时也获得了保护作用。还测试了用CELOa-VP2载体与纯化的VP2抗原、编码VP2的DNA或表达鸡髓样生长因子(cMGF)的CELO载体联合使用的初免 - 加强策略。与两次接种CELOa-VP2相比,这些方案均未显示能显著提高保护水平。这些结果表明,基于CELO的载体可用于在鸡中安全诱导针对超强毒力IBDV的强大保护性免疫。

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