PDF(Pubmed)
Abstract：
Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the ΔgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the ΔUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the ΔUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection.
摘要：
马术甲疱疹病毒1（EqAHV1）是一种已知引起呼吸道疾病的病毒病原体，神经综合征，和马匹的堕胎风暴。目前,目前还没有针对EqAHV1提供完全保护的疫苗。标记疫苗和感染和接种疫苗的动物的分化（DIVA）策略对于预防和控制爆发是有效的，但尚未用于预防EqAHV1感染。糖蛋白2（gp2），位于病毒（EqAHV1）的包膜上，表现出高抗原性并作为DIVA的分子标记。在这项研究中,一系列缺失gp2和其他毒力基因的EqAHV1突变体(TK，UL24/TK,gI/gE)被设计。在体外研究突变病毒,然后在体内实验中使用金叙利亚仓鼠来评估病毒减毒的程度和与野生型(WT)病毒相比由突变病毒引起的免疫应答。与WT菌株相比，YM2019Δgp2，ΔTK/gp2和ΔUL24/TK/gp2菌株在RK-13细胞中表现出降低的生长，而ΔgI/gE/gp2菌株表现出明显的增殖受损。YM2019Δgp2菌株在仓鼠中诱导临床症状和死亡。相比之下,YM2019ΔTK/gp2和ΔUL24/TK/gp2变体显示致病性减弱，没有可观察到的临床症状或死亡。用含有YM2019ΔTK/gp2和ΔUL24/TK/gp2的鼻疫苗免疫在仓鼠中引起强烈的免疫应答。特别是,与含有ΔTK/gp2菌株的疫苗相比，含有ΔUL24/TK/gp2毒株的疫苗在用WT病毒攻击时表现出增强的免疫保护。此外，建立并完善了gp2的ELISA，以准确区分感染和接种疫苗的动物。这些结果证实ΔUL24/TK/gp2菌株是用于控制EqAHV1感染的安全且有效的减毒活疫苗候选物。
