VHSV G glycoprotein major determinants implicated in triggering the host type I IFN antiviral response as DNA vaccine molecular adjuvants
VHSV G glycoprotein major determinants implicated in triggering the host type I IFN antiviral response as DNA vaccine molecular adjuvants
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DOI：
10.1016/j.vaccine.2014.07.111
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发表时间：
2014-10-14
期刊：
影响因子：
5.5
通讯作者：
Estepa, A.
中科院分区：
文献类型：
--
作者：
Martinez-Lopez, A.;Garcia-Valtanen, P.;Estepa, A.
我们最近确定了病毒性出血性败血症横纹肌病毒（gpG(VHSV)）糖蛋白G的两个主要决定因素，肽p31和p33涉及触发宿主与这些横纹肌病毒抗原相关的I型IFN抗病毒反应。为了研究这些病毒糖蛋白区域作为DNA分子佐剂的特性，将其相应的cDNA序列克隆到gpG（VHSV）信号肽和跨膜序列两侧的质粒（pMCV1.4）中。此外，还设计了一个同时编码p31和p33序列的质粒结构（pMCV1.4-p31 + p33）。体外短暂细胞转染实验表明，这些VHSV gpG区域能够诱导I型IFN刺激基因的表达，并赋予对不同鱼类横纹肌病毒（鲤春病毒血症）感染的抗性。在体内，斑马鱼肌肉注射仅1 μ g构建体pMCV1.4-p31 + p33，可在免疫后45天内保护鱼免受SVCV致命攻击。此外，pMCV1.4-p31 + p33构建物对基于该病毒表面抗原（pAE6-G(SVCV)）的SVCV DNA疫苗的分子佐剂性进行了检测。结果表明，SVCV DNA疫苗和分子佐剂的联合注射允许(i) pAE6-GSVCV的剂量减少10倍而不影响其效力（ii）增加保护时间，以及（iii）增加存活率。据我们所知，这是第一个利用病毒gpG的特异性ifn诱导区域来设计更有效和更具成本效益的病毒疫苗的报告，同时也提高了我们对如何刺激先天免疫系统的认识。2014爱思唯尔有限公司版权所有。
We have recently identified the two major determinants of the glycoprotein G of the viral hemorrhagic septicaemia rhabdovirus (gpG(VHSV)), peptides p31 and p33 implicated in triggering the host type I IFN antiviral response associated to these rhabdoviral antigens. With the aim to investigate the properties of these viral glycoprotein regions as DNA molecular adjuvants, their corresponding cDNA sequences were cloned into a plasmid (pMCV1.4) flanked by the signal peptide and transmembrane sequences of gpG(VHSV). In addition, a plasmid construct encoding both sequences p31 and p33 (pMCV1.4-p31 + p33) was also designed. In vitro transitory cell transfection assays showed that these VHSV gpG regions were able to induce the expression of type I IFN stimulated genes as well as to confer resistance to the infection with a different fish rhabdovirus, the spring viremia of carp virus (SVCV). In vivo, zebrafish intramuscular injection of only 1 mu g of the construct pMCV1.4-p31 + p33 conferred fish protection against SVCV lethal challenge up to 45 days post-immunization. Moreover, pMCV1.4-p31 + p33 construct was assayed for molecular adjuvantcity's for a DNA vaccine against SVCV based in the surface antigen of this virus (pAE6-G(SVCV)). The results showed that the co-injection of the SVCV DNA vaccine and the molecular adjuvant allowed (i) a ten-fold reduction in the dose of pAE6-GSVCV without compromising its efficacy (ii) an increase in the duration of protection, and (iii) an increase in the survival rate. To our knowledge, this is the first report in which specific IFN-inducing regions from a viral gpG are used to design more-efficient and cost-effective viral vaccines, as well as to improve our knowledge on how to stimulate the innate immune system. 0 2014 Elsevier Ltd. All rights reserved.