Chowdhury Shafiqul I, Wei Huiyong, Weiss Marcello, Pannhorst Katrin, Paulsen Daniel B
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, United States.
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, United States.
Vaccine. 2014 Sep 3;32(39):4909-15. doi: 10.1016/j.vaccine.2014.07.004. Epub 2014 Jul 24.
Bovine herpesvirus 1 (BoHV-1) causes respiratory infections and abortions in cattle, and is an important component of bovine respiratory disease complex, which causes a considerable economic loss worldwide. Several efforts have been made to produce safer and more effective vaccines. One of these vaccines is a glycoprotein E (gE)-deleted marker vaccine which is currently mandated for use in EU countries. In the present study, we have constructed a three-gene-mutated BoHV-1 vaccine virus (UL49.5 luminal domain residues 30-32 and cytoplasmic tail residues 80-96 deleted, gE cytoplasmic tail- and entire Us9-deleted) and compared its protective vaccine efficacy in calves after intranasal vaccination with that of a gE-deleted virus. Following vaccination, both the triple mutant and gE-deleted vaccine virus replicated well in the nasal epithelium of the calves. The vaccinated calves did not show any clinical signs. Four weeks post-vaccination, the animals were challenged intranasally with a virulent BoHV-1 wild-type virus. Based on clinical signs, both the gE-deleted and triple mutant group were protected equally against the virulent BoHV-1 challenge. However, based on the quantity and duration of nasal viral shedding, virus neutralizing antibody and cellular immune responses, the triple mutant virus vaccine induced a significantly better protective immune response than the gE-deleted virus vaccine. Notably, after the virulent BoHV-1 challenge, the triple mutant virus vaccinated group cleared the challenge virus three days earlier than the BoHV-1 gE-deleted virus vaccinated group.
牛疱疹病毒1型(BoHV-1)可引发牛的呼吸道感染和流产,是牛呼吸道疾病综合征的重要组成部分,在全球范围内造成相当大的经济损失。人们已做出多项努力来生产更安全、更有效的疫苗。其中一种疫苗是缺失糖蛋白E(gE)的标记疫苗,目前欧盟国家强制使用该疫苗。在本研究中,我们构建了一种三基因缺失的BoHV-1疫苗病毒(UL49.5腔结构域第30至32位残基和胞质尾第80至96位残基缺失,gE胞质尾和整个Us9缺失),并将其经鼻接种犊牛后的疫苗保护效力与缺失gE的病毒进行比较。接种疫苗后,三重突变体和缺失gE的疫苗病毒在犊牛鼻上皮中均能良好复制。接种疫苗的犊牛未表现出任何临床症状。接种疫苗四周后,给动物经鼻接种强毒BoHV-1野生型病毒。基于临床症状,缺失gE的组和三重突变体组对强毒BoHV-1攻击的保护效果相同。然而,基于鼻病毒排出量和持续时间、病毒中和抗体及细胞免疫反应,三重突变病毒疫苗诱导的保护性免疫反应明显优于缺失gE的病毒疫苗。值得注意的是,在强毒BoHV-1攻击后,接种三重突变病毒的组清除攻击病毒的时间比接种BoHV-1缺失gE病毒的组早三天。