Neutralizing epitopes mapping of human adenovirus type 14 hexon
Neutralizing epitopes mapping of human adenovirus type 14 hexon
复制标题
人腺病毒14型六邻体的中和表位作图
DOI：
10.1016/j.vaccine.2015.10.117
复制
发表时间：
2015-11-27
期刊：
影响因子：
5.5
通讯作者：
Zhou, Rong
中科院分区：
文献类型：
--
作者：
Ma, Qiang;Tian, Xingui;Zhou, Rong
人腺病毒14型（HAdV - 14）在民用和军事环境中均引发了多起急性呼吸道疾病（ARD）暴发。鉴定HAdV - 14的中和表位对于感染的监测和控制非常重要。由于先前的研究表明腺病毒中和表位可能暴露在六邻体表面，通过同源建模方法预测了四个表位肽，A14R1（残基141 - 157）、A14R2（残基181 - 189）、A14R4（残基252 - 260）和A14R7（残基430 - 442），并将它们定位到六邻体的三维结构上。然后合成了这四个肽，通过酶联免疫吸附测定（ELISA）和中和试验（NT），这四个假定的表位均被鉴定为中和表位。最后我们使用“抗原衣壳整合”策略将这四个表位整合到人腺病毒3型（HAdV - 3）载体中，成功获得了两种嵌合腺病毒A14R2A3和A14R4A3，它们分别在HAdV - 3病毒粒子的六邻体表面展示A14R2和A14R4。进一步分析表明，这两种嵌合病毒的抗血清能够中和HAdV - 14和HAdV - 3的感染。抗 - A14R4A3组的中和效价显著高于抗 - KLH - A14R4组（P = 0.0442）。这些发现对于开发基于肽的具有广泛保护作用的HAdV - 14和HAdV - 3二价疫苗具有重要意义。（C）2015爱思唯尔有限公司。保留所有权利。
Human adenoviruses 14 (HAdV-14) caused several clusters of acute respiratory disease (ARD) outbreaks in both civilian and military settings. The identification of the neutralizing epitopes of HAdV-14 is important for the surveillance and control of infection. Since the previous studies had indicated that the adenoviruses neutralizing epitopes were likely to be exposed on the surface of the hexon, four epitope peptides, A14R1 (residues 141-157), A14R2 (residues 181-189), A14R4 (residues 252-260) and A14R7 (residues 430-442) were predicted and mapped onto the 3D structures of hexon by homology modeling approach. Then the four peptides were synthesized, and all the four putative epitopes were identified as neutralizing epitopes by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally we incorporated the four epitopes into human adenoviruses 3 (HAdV-3) vectors using the "antigen capsid-incorporation" strategy, and two chimeric adenoviruses, A14R2A3 and A14R4A3, were successfully obtained which displayed A14R2 and A14R4 respectively on the hexon surface of HAdV-3 virions. Further analysis showed that the two chimeric viruses antiserum could neutralize both HAdV-14 and HAdV-3 infection. The neutralization titers of anti-A14R4A3 group were significantly higher than the anti-KLH-A14R4 group (P=0.0442). These findings have important implications for the development of peptide-based broadly protective HAdV-14 and HAdV-3 bivalent vaccine. (C) 2015 Elsevier Ltd. All rights reserved.