A lumpy skin disease virus deficient of an IL-10 gene homologue provides protective immunity against virulent capripoxvirus challenge in sheep and goats
A lumpy skin disease virus deficient of an IL-10 gene homologue provides protective immunity against virulent capripoxvirus challenge in sheep and goats
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DOI：
10.1016/j.antiviral.2015.08.016
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发表时间：
2015-11-01
影响因子：
7.6
通讯作者：
Babiuk, Shawn
中科院分区：
文献类型：
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作者：
Boshra, Hani;Thang Truong;Babiuk, Shawn
绵羊和山羊痘仍然是重要的牲畜疾病，对非洲和亚洲许多地区的畜牧业构成重大威胁。目前，有几种减毒活疫苗可供使用，并在流行国家用于控制这些疾病。其中一种是肿块性皮肤病病毒（LSDV）的部分减毒株KS-1，它提供对绵羊痘和山羊痘的交叉保护。然而，当在高度应激的奶牛中使用疫苗来预防肿块性皮肤病（LSD）时，疫苗可能导致临床疾病。为了开发对这三种疾病都有效的更安全的疫苗，研究人员利用基因敲除（KO）技术去除一种假定的毒力因子基因（il -10样基因），从而对一株LSDV致病菌株（南非Warmbaths [WB]）进行了减毒。该构建体（LSDV WB005K0）随后被评估为绵羊和山羊抗强毒性卡波病毒攻击的疫苗。用该构建体接种绵羊和山羊，观察21 d。该疫苗似乎是安全的，并且不会引起疾病，尽管它在注射部位引起轻微炎症，类似于其他减毒绵羊和山羊痘疫苗引起的炎症。此外，在接种疫苗后使用实时PCR在血液、口腔或鼻拭子中未检测到病毒复制，并且在绵羊和山羊中均检测到低水平的中和抗体。接种疫苗后，从接种疫苗的动物中分离出的白细胞可诱导卡帕痘病毒特异性ifn - γ分泌，表明免疫也是t细胞介导的。在强毒性的卡波病毒攻击后，接种疫苗的绵羊和山羊被发现完全受到保护，没有表现出临床疾病。此外，对不同时间点的血液样本进行实时PCR检测表明，两组接种疫苗的动物均未出现病毒血症，而未接种疫苗的动物则未出现与卡波病毒相关的临床疾病和病毒血症。这些发现表明，这种新的LSDV敲除菌株有潜力作为一种疫苗来保护牲畜免受绵羊痘和山羊痘的侵害。Elsevier B.V.版权所有
Sheep and goat pox continue to be important livestock diseases that pose a major threat to the livestock industry in many regions in Africa and Asia. Currently, several live attenuated vaccines are available and used in endemic countries to control these diseases. One of these is a partially attenuated strain of lumpy skin disease virus (LSDV), KS-1, which provides cross-protection against both sheep pox and goat pox. However, when used in highly stressed dairy cattle to protect against lumpy skin disease (LSD) the vaccine can cause clinical disease. In order to develop safer vaccines effective against all three diseases, a pathogenic strain of LSDV (Warmbaths [WB], South Africa) was attenuated by removing a putative virulence factor gene (IL-10-like) using gene knockout (KO) technology. This construct (LSDV WB005K0) was then evaluated as a vaccine for sheep and goats against virulent capripoxvirus challenge. Sheep and goats were vaccinated with the construct and the animals were observed for 21 days. The vaccine appeared to be safe, and did not cause disease, although it induced minor inflammation at the injection site similar to that caused by other attenuated sheep and goat pox vaccines. In addition, no virus replication was detected in blood, oral or nasal swabs using real-time PCR following vaccination and low levels of neutralising antibodies were detected in both sheep and goats. Leukocytes isolated from vaccinated animals following vaccination elicited capripoxvirus-specific IFN-gamma secretion, suggesting that immunity was also T-cell mediated. Following challenge with virulent capripoxvirus, vaccinated sheep and goats were found to be completely protected and exhibited no clinical disease. Furthermore, real-time PCR of blood samples at various time points suggested that viremia was absent in both groups of vaccinated animals, as opposed to capripoxvirus-related clinical disease and viremia observed in the unvaccinated animals. These findings suggest that this novel knockout strain of LSDV has potential as a vaccine to protect livestock against sheep pox and goat pox. Crown Copyright 0 2015 Published by Elsevier B.V. All rights reserved.