Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin 150001, China.
J Virol Methods. 2013 Mar;188(1-2):175-82. doi: 10.1016/j.jviromet.2012.08.021. Epub 2012 Sep 4.
The objective of this study was to explore the immunogenicity of an adenovirus construction expressing a type O foot and mouth disease virus neutralising epitope (8E8) in the context of heterologous capsid proteins. Adenoviruses expressing four chimeric type Asia1 FMDV capsid proteins were constructed by inserting the type O FMDV 8E8 epitope into the G-H loop from the type Asia1 VP1 at amino acid residues 139/140, 150/151, 134/140 or at both 139/140 and 150/151. These recombinant proteins were recognised by antibodies against the type O 8E8 epitope and type Asia1 FMDV. When inoculated in mice, all of the recombinant chimeric capsid proteins for each single epitope insertion induced the production of anti-type O FMDV neutralising antibodies. The recombinant chimeric capsid proteins with a foreign insertion at position 139/140 or 150/151 induced high levels of anti-type Asia1 FMDV neutralising antibodies as the recombinant type Asia1 capsid proteins without any foreign epitope, suggesting that the foreign insertion did not affect the immunogenicity of the type Asia1 FMDV capsid proteins. This study suggests that a foreign epitope displayed on the surface of the FMDV capsid proteins could induce an epitope-specific response. Therefore, the adenovirus-vectored FMDV capsid proteins could be used as a vehicle for the development of an epitope-based vaccine.
本研究旨在探索表达口蹄疫病毒(FMDV)O 型中和表位(8E8)的腺病毒构建体在异源衣壳蛋白背景下的免疫原性。通过将 FMDV O 型 8E8 表位插入到 VP1 的 G-H 环中,在氨基酸残基 139/140、150/151、134/140 或 139/140 和 150/151 处构建了表达四种嵌合型亚洲 1 型 FMDV 衣壳蛋白的腺病毒。这些重组蛋白被针对 O 型 8E8 表位和亚洲 1 型 FMDV 的抗体识别。当在小鼠中接种时,每个单一位点插入的重组嵌合衣壳蛋白均诱导产生针对 O 型 FMDV 的中和抗体。在位置 139/140 或 150/151 处插入外源表位的重组嵌合衣壳蛋白诱导产生高水平的针对亚洲 1 型 FMDV 的中和抗体,与不携带任何外源表位的重组亚洲 1 型衣壳蛋白相当,表明外源插入不影响亚洲 1 型 FMDV 衣壳蛋白的免疫原性。本研究表明,在 FMDV 衣壳蛋白表面展示的外源表位可诱导表位特异性反应。因此,腺病毒载体 FMDV 衣壳蛋白可作为开发基于表位疫苗的载体。