A DNA vaccine encoding ubiquitinated Rift Valley fever virus nucleoprotein provides consistent immunity and protects IFNAR-/- mice upon lethal virus challenge
A DNA vaccine encoding ubiquitinated Rift Valley fever virus nucleoprotein provides consistent immunity and protects IFNAR-/- mice upon lethal virus challenge
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DOI：
10.1016/j.vaccine.2011.04.043
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发表时间：
2011-06-15
期刊：
影响因子：
5.5
通讯作者：
Brun, Alejandro
中科院分区：
文献类型：
--
作者：
Boshra, Hani;Lorenzo, Gema;Brun, Alejandro
目前针对裂谷热病毒（RVFV）的候选疫苗将病毒结构糖蛋白作为抗原，因为触发针对它们的抗体应答通常与保护相关。在这里，我们只关注RVFV的核蛋白作为疫苗开发的潜在靶点。先前在小鼠模型中的研究已经证明，RVFV核蛋白在通过DNA疫苗或以重组可溶性蛋白形式施用时可以引起部分保护。为了确定这种部分保护性免疫应答是否可以增强到与编码RVFV糖蛋白的DNA构建体相当的水平，将几个靶向序列克隆到RVFV核蛋白（N）基因附近。用编码病毒核蛋白的泛素化形式的质粒构建体（pCMV-Ub-N）免疫，显著增加IFNAR（-/-）小鼠在病毒攻击后的存活率，达到与编码两种RVFV糖蛋白的重组DNA疫苗相当的水平。用pCMV-Ub-N免疫的小鼠也显示出更高水平的非中和性抗N抗体和抗原特异性T细胞应答。这表明其他细胞介导的应答在针对RVFV的保护中的作用。这些发现显示RVFV N作为疫苗接种的候选抗原的潜力，并提出了针对某些布尼亚病毒的疫苗设计的新策略，其中糖蛋白变异可能会阻碍有效的广泛疫苗接种策略。(C)2011爱思唯尔有限公司保留所有权利。
Current vaccine candidates against Rift Valley fever virus (RVFV) incorporate the viral structural glycoproteins as antigens, since triggering antibody responses against them usually correlates with protection. Here, we have focused solely on the nucleoprotein of RVFV as a potential target for vaccine development. Previous studies in mouse models have already demonstrated that RVFV nucleoprotein can elicit partial protection when administered by means of a DNA vaccine or in recombinant, soluble, protein form. To determine whether this partially protective immune response could be augmented to a level comparable to DNA constructs encoding for RVFV glycoproteins, several targeting sequences were cloned adjacent to the RVFV nucleoprotein (N) gene. Immunization with a plasmid construct encoding for a ubiquitinated form of the viral nucleoprotein (pCMV-Ub-N) significantly increased the survival of IFNAR(-/-) mice following viral challenge to levels comparable with a recombinant DNA-vaccine encoding both RVFV glycoproteins. Mice immunized with pCMV-Ub-N also displayed higher levels of non-neutralizing anti-N antibodies and antigen-specific T-cell responses. This suggests a role for other cell mediated responses in protection against RVFV. These findings show the potential of RVFV N as a candidate antigen for vaccination, and present a new strategy in vaccine design against certain bunyaviruses, where glycoprotein variation may impede effective broad-based vaccination strategies. (C) 2011 Elsevier Ltd. All rights reserved.