Ma Qiang, Tian Xingui, Jiang Zaixue, Huang Junfeng, Liu Qian, Lu Xiaomei, Luo Qingming, Zhou Rong
State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, China; Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, China.
Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan 523325, China.
Vaccine. 2015 Nov 27;33(48):6659-65. doi: 10.1016/j.vaccine.2015.10.117. Epub 2015 Nov 3.
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.
人腺病毒14型（HAdV-14）在民用和军事环境中引发了几起急性呼吸道疾病（ARD）集群性疫情。鉴定HAdV-14的中和表位对于感染的监测和控制至关重要。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，即A14R1（第141 - 157位氨基酸残基）、A14R2（第181 - 189位氨基酸残基）、A14R4（第252 - 260位氨基酸残基）和A14R7（第430 - 442位氨基酸残基），并将其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）确定所有这四个推定表位均为中和表位。最后，我们采用“抗原衣壳掺入”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，这两种嵌合病毒抗血清能够中和HAdV-14和HAdV-3感染。抗A-14R4A3组的中和效价显著高于抗KLH-A14R4组（P = 0.0442）。这些发现对于基于肽的HAdV-14和HAdV-3广谱保护性二价疫苗的开发具有重要意义。
