A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus
A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus
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DOI：
10.1016/j.vaccine.2016.03.015
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发表时间：
2016-04-19
期刊：
影响因子：
5.5
通讯作者：
Saiz, Juan-Carlos
中科院分区：
文献类型：
--
作者：
Martin-Acebes, Miguel A.;Blazquez, Ana-Belen;Saiz, Juan-Carlos
乌苏图病毒 (USUV) 是一种蚊媒黄病毒，自 1959 年首次发现以来，其传播仅限于非洲。然而，在过去十年中，USUV 在欧洲出现，导致禽类死亡和人类零星严重神经侵袭性感染。值得注意的是，成年实验室小鼠对 USUV 感染的敏感性有限，这损害了免疫反应的分析，从而使病毒宿主相互作用和针对该病原体的候选疫苗的评估变得复杂。在这项工作中，我们证明了α/β干扰素受体缺陷的小鼠（IFNAR (-/-)小鼠）对USUV感染高度敏感，并为疫苗测试提供了致死攻击模型。验证该感染模型；设计了编码 USUV 膜前体 (prM) 和包膜 (E) 蛋白的质粒 DNA 候选疫苗。用该质粒转染培养细胞导致 USUV 抗原表达以及小病毒样颗粒（也称为重组亚病毒颗粒 (RSPB)）的组装和分泌。使用该质粒进行单次肌内免疫足以在 IFNAR (-/-) 小鼠中引发显着水平的针对 USUV 攻击的保护作用。所诱导的体液反应的特征表明，DNA 疫苗接种引发了抗 USUV 抗体，包括中和抗体。总体而言，这些结果探讨了 IFNAR (-/-) 小鼠作为适合研究 USUV 宿主病毒相互作用和疫苗测试的小动物模型的适用性，以及基于 DNA 的疫苗策略控制这种病原体的可行性。 (C) 2016 Elsevier Ltd. 保留所有权利。
Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model; a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPB). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen. (C) 2016 Elsevier Ltd. All rights reserved.