Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen
Immunization of knock-out α/β interferon receptor mice against lethal bluetongue infection with a BoHV-4-based vector expressing BTV-8 VP2 antigen
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DOI：
10.1016/j.vaccine.2011.01.075
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发表时间：
2011-04-05
期刊：
影响因子：
5.5
通讯作者：
Donofrio, Gaetano
中科院分区：
文献类型：
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作者：
Franceschi, Valentina;Capocefalo, Antonio;Donofrio, Gaetano
新的有效的疫苗策略工具是必要的，以限制蓝舌病，一种昆虫传播的病毒性疾病的家庭和野生反刍动物的传播。在本研究中。将克隆为细菌人工染色体（BAC）的基于BoHV-4的载体工程化以表达蓝舌病毒（BTV）免疫显性糖蛋白VP 2，其氨基末端提供异源信号肽，羧基末端提供跨膜结构域（IgK-VP 2gDtm），以允许VP 2表达靶向细胞膜部分。基于新产生的蓝舌病实验动物模型成年α/β干扰素受体敲除（IFNAR（（-/-）小鼠，进行攻击前实验以测试BoHV-4在该免疫受损动物上的安全性。即使在脑内接种BoHV-4后，BoHV-4感染的IFNAR（（-/-））小鼠也没有显示出临床体征，尽管脑的许多区域被转导。在不同时间点用BoHV-4-A-IgK-VP 2gDtm腹膜内接种两次的IFNAR（（-/-））小鼠产生了针对BTV的血清中和抗体，并且当用致死剂量的BTV-8攻击时，显示出病毒血症的强烈降低和更长的存活时间。在该初步研究中获得的数据验证了基于BoHV-4的载体作为安全有效的异源抗原载体/生产者，用于配制用于针对致死性蓝舌病的疫苗接种的增强的重组免疫原。(C)2011爱思唯尔有限公司保留所有权利。
New effective tools for vaccine strategies are necessary to limit the spread of bluetongue, an insect-transmitted viral disease of domestic and wild ruminants. In the present study. BoHV-4-based vector cloned as a bacterial artificial chromosome (BAC) was engineered to express the bluetongue virus (BTV) immune-dominant glycoprotein VP2 provided of a heterologous signal peptide to its amino terminal and a trans-membrane domain to its carboxyl terminal (IgK-VP2gDtm), to allow the VP2 expression targeting to the cell membrane fraction. Based on adult alpha/beta interferon receptor knockout (IFNAR((-/-))) mice, a newly generated bluetongue laboratory animal model, a pre-challenge experiment was performed to test BoHV-4 safety on such immune-compromised animal. BoHV-4 infected IFNAR((-/-)) mice did not show clinical signs even following the inoculation of BoHV-4 intra-cerebrally, although many areas of the brain got transduced. IFNAR((-/-)) mice intraperitoneally inoculated twice with BoHV-4-A-IgK-VP2gDtm at different time points developed serum neutralizing antibodies against BTV and showed a strongly reduced viremia and a longer survival time when challenged with a lethal dose of BTV-8. The data acquired in this pilot study validate BoHV-4-based vector as a safe and effective heterologous antigen carrier/producer for the formulation of enhanced recombinant immunogens for the vaccination against lethal bluetongue. (C) 2011 Elsevier Ltd. All rights reserved.