Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines.
Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines.
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DOI：
10.1128/jvi.01892-16
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发表时间：
2017-01-01
影响因子：
5.4
通讯作者：
Roy P
中科院分区：
文献类型：
--
作者：
Celma CC;Stewart M;Wernike K;Eschbaumer M;Gonzalez-Molleda L;Breard E;Schulz C;Hoffmann B;Haegeman A;De Clercq K;Zientara S;van Rijn PA;Beer M;Roy P
蓝舌病病毒（BTV）是世界上许多地方的地方病，常引起家畜严重的出血性疾病。迄今为止，至少有27种不同的血清型已被确认。针对所有血清型的疫苗接种是必要的，以保护易感动物，并防止病毒通过昆虫媒介继续传播。在我们以前的研究中，我们为许多血清型产生了复制缺陷型（丧失感染性单循环[DISC]）病毒株，并报告了其在动物中保护效力的初步数据。在本报告中，为了将DISC疫苗推向市场，我们研究了这些DISC疫苗的不同参数。首先，我们证明了这些疫苗株和补充细胞系的遗传稳定性。随后，确定了疫苗的最佳储存条件，包括添加剂、温度和干燥，并确认了其在动物中的保护效力。此外，为了测试不同疫苗株的混合物是否可以耐受，我们在绵羊和牛（BTV的两种天然宿主）中测试了三种或六种不同血清型组合的DISC疫苗的混合物。用六种不同疫苗的混合物接种的绵羊组在早期攻毒和攻毒5个月后均完全免受单个强毒血清型的攻毒，且无任何临床疾病。不同疫苗之间的保护没有干扰。在牛中也用三种疫苗株的混合物实现了保护，尽管水平低于绵羊。我们的数据支持并验证了这些病毒株作为BTV下一代疫苗的适用性。重要信息蓝舌病（BT）是一种使人衰弱的疾病，在许多情况下是致命的疾病，影响反刍动物的经济重要性。提供针对蓝舌病病毒（病原体）的保护的经典疫苗并非没有继发性和不良反应。在BTV反向遗传学系统开发之后，生产高度减毒，更安全疫苗的新方法激增，该系统允许在病毒基因组中引入靶向突变。我们瞄准了一个关键基因，以开发作为候选疫苗的残疾病毒株。本报告中的结果进一步证实了我们以前的证据，并支持这些病毒株作为下一代BTV疫苗的适用性。
Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines.