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利用自组装 ADDomer 平台展示 O 型口蹄疫病毒的 B 和 T 表位。

Using Self-Assembling ADDomer Platform to Display B and T Epitopes of Type O Foot-and-Mouth Disease Virus.

机构信息

College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China.

Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China.

出版信息

Viruses. 2022 Aug 18;14(8):1810. doi: 10.3390/v14081810.

Abstract

Foot-and-mouth disease virus (FMDV) is a highly contagious and devastating virus that infects cloven-hoofed livestock and various wildlife species. Vaccination is the best measure to prevent FMD. ADDomer, as a kind of non-infectious adenovirus-inspired nanoparticle, has the advantage of high thermal stability. In this study, two dominant B-cell antigen epitopes (residues 129160 and 200213) and a dominant T-cell antigen epitope (residues 16~44) of type O FMDV were inserted into the ADDomer variable loop (VL) and arginine-glycine-aspartic acid (RGD) loop. The 3D structure of the recombinant protein (ADDomer-RBT) was simulated by homology modeling. First, the recombinant proteins were expressed by the baculovirus expression system and detected by western blot and Q Exactive mass spectrometry. Then the formation of VLPs was observed under a transmission electron micrograph (TEM). Finally, we evaluated the immunogenicity of chimeric VLPs with a murine model. Bioinformatic software analysis preliminarily corroborated that the chosen epitopes were successfully exposed on the surface of ADDomer VLPs. The TEM assay demonstrated the structural integrity of the VLPs. After immunizing, it was found that FMDV-specific antibodies can be produced in mice to induce humoral and cellular immune responses. To sum up, the ADDomer platform can be used as an effective antigen carrier to deliver antigen epitopes. This study presents one of the candidate vaccines to prevent and control FMDV.

摘要

口蹄疫病毒(FMDV)是一种高度传染性和破坏性的病毒,感染有蹄类动物和各种野生动物。接种疫苗是预防 FMD 的最佳措施。ADDomer 是一种非传染性的腺病毒启发的纳米颗粒,具有高热稳定性的优势。在这项研究中,两种主要的 B 细胞抗原表位(残基 129160 和 200213)和一种主要的 T 细胞抗原表位(残基 16~44)被插入到 ADDomer 可变环(VL)和精氨酸-甘氨酸-天冬氨酸(RGD)环中。通过同源建模模拟了重组蛋白(ADDomer-RBT)的 3D 结构。首先,通过杆状病毒表达系统表达重组蛋白,并通过 Western blot 和 Q Exactive 质谱进行检测。然后,在透射电子显微镜(TEM)下观察 VLPs 的形成。最后,我们用小鼠模型评估嵌合 VLPs 的免疫原性。生物信息学软件分析初步证实,所选的表位成功地暴露在 ADDomer VLPs 的表面。TEM 检测表明 VLPs 的结构完整。免疫后,发现小鼠体内可以产生 FMDV 特异性抗体,诱导体液和细胞免疫反应。总之,ADDomer 平台可作为一种有效的抗原载体来传递抗原表位。本研究提供了一种预防和控制 FMDV 的候选疫苗。

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