Characterization of protection afforded by a bivalent virus-like particle vaccine against bluetongue virus serotypes 1 and 4 in sheep.
Characterization of protection afforded by a bivalent virus-like particle vaccine against bluetongue virus serotypes 1 and 4 in sheep.
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DOI：
10.1371/journal.pone.0026666
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Roy P
中科院分区：
文献类型：
--
作者：
Pérez de Diego AC;Athmaram TN;Stewart M;Rodríguez-Sánchez B;Sánchez-Vizcaíno JM;Noad R;Roy P
蓝舌病毒(BTV)是欧洲一种重要的节肢动物传播的新兴病原体，主要在绵羊和牛身上引起疾病。蓝舌病的常规疫苗接种将需要能够区分接种疫苗的人和感染的人(DIVA)。目前的疫苗是有效的，但不是天后。病毒样颗粒(VLP)是高度免疫原性的病毒颗粒的结构模拟物，只包含自然感染中存在的蛋白质的一部分。因此，VLP为开发与DIVA相容的蓝舌疫苗提供了潜力。用BTV-1VLP单价疫苗或BTV-1VLP和BTV-4VLP的双价混合物免疫美利奴绵羊，并用BTV-1或BTV-4强毒攻击。监测动物的临床体征、抗体反应和病毒RNA。19/20只BTV-1 VLP单独或与BTV-4 VLP联合免疫的动物产生了BTV-1的中和抗体和BTV VP7的群特异性抗体。没有表现出可检测到的中和抗体或组特异性抗体的一只动物，在攻击后有可检测到的病毒RNA，但在与强毒BTV-1攻击时没有表现出任何临床症状。相比之下，所有对照动物在受到相同病毒攻击时都表现出蓝舌病的典型临床症状。六只动物接种了双价疫苗，并用BTV-4毒力攻击，其中两只动物的病毒RNA水平可检测到，其中一只显示出与BTV感染一致的临床症状并死亡。有很好的证据表明，BTV-1 VLP作为单价或双价免疫原递送，可在与强毒BTV-1共同攻击时保护蓝舌病。然而，BTV-1和BTV-4VLP双价疫苗对BTV-4的保护性应答可能存在一定的干扰。这就提出了一个问题：双价BTV疫苗的所有组合是否都是可能的，或者特定血清型的免疫优势是否会干扰疫苗的效力。
Bluetongue virus (BTV) is an economically important, arthropod borne, emerging pathogen in Europe, causing disease mainly in sheep and cattle. Routine vaccination for bluetongue would require the ability to distinguish between vaccinated and infected individuals (DIVA). Current vaccines are effective but are not DIVA. Virus-like particles (VLPs) are highly immunogenic structural mimics of virus particles, that only contain a subset of the proteins present in a natural infection. VLPs therefore offer the potential for the development of DIVA compatible bluetongue vaccines. Merino sheep were vaccinated with either monovalent BTV-1 VLPs or a bivalent mixture of BTV-1 VLPs and BTV-4 VLPs, and challenged with virulent BTV-1 or BTV-4. Animals were monitored for clinical signs, antibody responses, and viral RNA. 19/20 animals vaccinated with BTV-1 VLPs either alone or in combination with BTV-4 VLPs developed neutralizing antibodies to BTV-1, and group specific antibodies to BTV VP7. The one animal that showed no detectable neutralizing antibodies, or group specific antibodies, had detectable viral RNA following challenge but did not display any clinical signs on challenge with virulent BTV-1. In contrast, all control animals' demonstrated classical clinical signs for bluetongue on challenge with the same virus. Six animals were vaccinated with bivalent vaccine and challenged with virulent BTV-4, two of these animals had detectable viral levels of viral RNA, and one of these showed clinical signs consistent with BTV infection and died. There is good evidence that BTV-1 VLPs delivered as monovalent or bivalent immunogen protect from bluetongue disease on challenge with virulent BTV-1. However, it is possible that there is some interference in protective response for BTV-4 in the bivalent BTV-1 and BTV-4 VLP vaccine. This raises the question of whether all combinations of bivalent BTV vaccines are possible, or if immunodominance of particular serotypes could interfere with vaccine efficacy.