National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada.
CSIRO Biosecurity Flagship, Australian Animal Health Laboratory, Geelong, Australia.
Antiviral Res. 2015 Nov;123:39-49. doi: 10.1016/j.antiviral.2015.08.016. Epub 2015 Sep 1.
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 WB005KO) 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 21days. 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-γ 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.
绵羊痘和山羊痘仍然是重要的家畜疾病,对非洲和亚洲许多地区的畜牧业构成重大威胁。目前,一些减毒活疫苗在流行国家被用于控制这些疾病。其中一种是一种部分减毒的块状皮肤病病毒(LSDV)KS-1 株,它对绵羊痘和山羊痘都提供交叉保护。然而,当用于高度应激的奶牛以预防块状皮肤病(LSD)时,疫苗会引起临床疾病。为了开发针对所有三种疾病更安全的有效疫苗,使用基因敲除(KO)技术从一种致病性 LSDV(南非 Warmbaths [WB])株中去除了一个假定的毒力因子基因(IL-10 样),从而对其进行了减毒。该构建体(LSDV WB005KO)随后被评估为针对绵羊和山羊的针对强毒羊痘病毒挑战的疫苗。用该构建体对绵羊和山羊进行了疫苗接种,并对动物进行了 21 天的观察。疫苗似乎是安全的,不会引起疾病,尽管它在注射部位引起了类似于其他减毒绵羊痘和山羊痘疫苗引起的轻微炎症。此外,在用实时 PCR 检测接种后血液、口腔或鼻腔拭子中没有检测到病毒复制,并且在绵羊和山羊中均检测到低水平的中和抗体。接种疫苗后从接种动物中分离的白细胞可引发羊痘病毒特异性 IFN-γ 分泌,这表明免疫也是由 T 细胞介导的。在接受强毒羊痘病毒攻击后,接种疫苗的绵羊和山羊被发现完全受到保护,没有临床疾病。此外,在不同时间点对血液样本进行实时 PCR 检测表明,两组接种动物均不存在病毒血症,而未接种动物则出现了与羊痘病毒相关的临床疾病和病毒血症。这些发现表明,这种新型 LSDV 敲除株具有作为疫苗保护家畜免受绵羊痘和山羊痘的潜力。