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Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle

机译:实验性DIVA亚基疫苗对牛的蓝舌病毒血清型8的强保护作用

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Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This SW subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
机译:反刍动物中的蓝舌病毒(BTV)感染构成了永久性的农业威胁,因为新的血清型在新的地点不断出现。临床疾病主要在绵羊中观察到,但是在欧洲爆发BTV seroype 8(BTV-8)期间,牛受到了不同寻常的影响。我们先前开发了一种实验疫苗,该疫苗基于BTV-8的重组病毒蛋白2(VP2)和BTV-2的非结构蛋白1(NS1)和NS2,并混合了免疫刺激复合物(ISCOM)-基质佐剂。我们证明了这种疫苗诱导的牛免疫应答与经典的商业灭活疫苗诱导的牛免疫应答一样好或更高。在这项研究中,我们评估了实验疫苗在牛中的保护功效,并基于VP7抗体的检测,评估了病毒攻击后其DIVA的顺应性。两组BTV血清阴性的小牛以亚单位疫苗(n = 6)或仅以佐剂(n = 6)隔3周皮下免疫两次。在第二次免疫后3周进行BTV8攻击后,对照组出现了病毒血症和发烧,并伴有蓝舌病的其他轻度临床症状,而接种疫苗的动物受到了临床和病毒学保护。疫苗诱导的保护作用可能是由针对VP2的高病毒中和抗体滴度介导的,也可能是由对NS1和NS2的细胞反应介导的。 T淋巴细胞反应在BTV-2和BTV-8之间发生交叉反应,这表明NS1和NS2可能提供了一种适应性疫苗的基础,该疫苗可以通过使用不同血清型的VP2进行改变。攻击后在接种疫苗的动物和对照组中检测到不同水平的VP7抗体,表明疫苗与DIVA伴随测试之间存在一致性。该SW亚单位疫苗是有前途的候选物,应进一步评估和开发以保护其免受不同血清型的侵袭。 (C)2014作者。由Elsevier Ltd.发布。这是CC BY-NC-ND许可下的开放获取文章

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