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用缺失糖蛋白E的1型牛疱疹病毒标记株作为灭活疫苗或减毒活疫苗在牛中诱导的保护作用。

Protection induced by a glycoprotein E-deleted bovine herpesvirus type 1 marker strain used either as an inactivated or live attenuated vaccine in cattle.

作者信息

Romera Sonia Alejandra, Puntel Mariana, Quattrocchi Valeria, Del Médico Zajac Paula, Zamorano Patricia, Blanco Viera Javier, Carrillo Consuelo, Chowdhury Shafiqul, Borca Manuel V, Sadir Ana M

机构信息

Instituto de Virología Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias (CICV), Instituto Nacional de Tecnología Agropecuaria (INTA), Castelar, CC77, 1708 Morón, Argentina.

出版信息

BMC Vet Res. 2014 Jan 8;10:8. doi: 10.1186/1746-6148-10-8.

Abstract

BACKGROUND

Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections; causing a high economic loss in all continents. Use of marker vaccines in IBR eradication programs is widely accepted since it allows for protection of the animals against the disease while adding the possibility of differentiating vaccinated from infected animals.The aim of the present study was the development and evaluation of safety and efficacy of a glycoprotein E-deleted (gE-) BoHV-1 marker vaccine strain (BoHV-1ΔgEβgal) generated by homologous recombination, replacing the viral gE gene with the β-galactosidase (βgal) gene.

RESULTS

In vitro growth kinetics of the BoHV-1ΔgEβgal virus was similar to BoHV-1 LA. The immune response triggered by the new recombinant strain in cattle was characterized both as live attenuated vaccine (LAV) and as an inactivated vaccine. BoHV-1ΔgEβgal was highly immunogenic in both formulations, inducing specific humoral and cellular immune responses. Antibody titers found in animals vaccinated with the inactivated vaccine based on BoHV-1ΔgEβgal was similar to the titers found for the control vaccine (BoHV-1 LA). In the same way, titers of inactivated vaccine groups were significantly higher than any of the LAV immunized groups, independently of the inoculation route (p < 0.001). Levels of IFN-γ were significantly higher (p < 0.001) in those animals that received the LAV compared to those that received the inactivated vaccine. BoHV-1ΔgEβgal exhibited an evident attenuation when administered as a LAV; no virus was detected in nasal secretions of vaccinated or sentinel animals during the post-vaccination period. BoHV-1ΔgEβgal, when used in either formulation, elicited an efficient immune response that protected animals against challenge with virulent wild-type BoHV-1. Also, the deletion of the gE gene served as an immunological marker to differentiate vaccinated animals from infected animals. All animals vaccinated with the BoHV-1ΔgE βgal strain were protected against disease after challenge and shed significantly less virus than control calves, regardless of the route and formulation they were inoculated.

CONCLUSIONS

Based on its attenuation, immunogenicity and protective effect after challenge, BoHV-1ΔgEβgal virus is an efficient and safe vaccine candidate when used either as inactivated or as live attenuated forms.

摘要

背景

牛疱疹病毒1型(BoHV-1)是呼吸道和生殖道感染的病原体,在各大洲均造成高额经济损失。在传染性牛鼻气管炎根除计划中使用标记疫苗已被广泛接受,因为它既能保护动物免受疾病侵害,又能区分接种疫苗的动物和感染动物。本研究的目的是开发和评估通过同源重组产生的缺失糖蛋白E(gE-)的BoHV-1标记疫苗株(BoHV-1ΔgEβgal)的安全性和有效性,该疫苗株用β-半乳糖苷酶(βgal)基因取代了病毒的gE基因。

结果

BoHV-1ΔgEβgal病毒的体外生长动力学与BoHV-1 LA相似。新的重组毒株在牛体内引发的免疫反应兼具减毒活疫苗(LAV)和灭活疫苗的特征。BoHV-1ΔgEβgal在两种剂型中均具有高度免疫原性,可诱导特异性体液免疫和细胞免疫反应。用基于BoHV-1ΔgEβgal的灭活疫苗接种的动物体内发现的抗体滴度与对照疫苗(BoHV-1 LA)的滴度相似。同样,灭活疫苗组的滴度显著高于任何LAV免疫组,与接种途径无关(p < 0.001)。与接受灭活疫苗的动物相比,接受LAV的动物体内的IFN-γ水平显著更高(p < 0.001)。当作为LAV给药时,BoHV-1ΔgEβgal表现出明显的减毒;在疫苗接种后的时期内,在接种疫苗的动物或哨兵动物的鼻分泌物中未检测到病毒。当以任何一种剂型使用时,BoHV-1ΔgEβgal都能引发有效的免疫反应,保护动物免受强毒野生型BoHV-1的攻击。此外,gE基因的缺失作为一种免疫标记,可区分接种疫苗的动物和感染动物。所有接种BoHV-1ΔgE βgal株疫苗的动物在攻毒后均受到疾病保护,且病毒排出量明显低于对照小牛,无论接种途径和剂型如何。

结论

基于其减毒、免疫原性和攻毒后的保护作用,BoHV-1ΔgEβgal病毒无论是作为灭活疫苗还是减毒活疫苗使用,都是一种高效且安全的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bafa/3896737/ed7839002ead/1746-6148-10-8-1.jpg

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