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基于牛乳头瘤病毒 6 型的免疫原性嵌合病毒样颗粒的研制。

Development of immunogenic chimeric virus-like particles based on bovine papillomavirus type 6.

机构信息

National Institute of Animal Health, NARO, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.

Advanced Analysis Center, NARO, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8518, Japan.

出版信息

Vaccine. 2020 Nov 17;38(49):7774-7779. doi: 10.1016/j.vaccine.2020.10.037. Epub 2020 Oct 22.

Abstract

Virus-like particles (VLPs) are considered useful tools for vaccine development because they induce an immune response and are safe. In addition, VLPs may be useful as a platform for the presentation of foreign antigens to elicit immune responses. In this study, we aimed to produce a chimeric VLP composed of L1 protein of bovine papillomavirus type 6 (BPV6-L1) that can display an entire foreign protein on its surface. Based on prediction of the conformational structure of VLP of BPV6-L1 (BPV6-VLP), candidate insertion sites for the foreign protein into BPV6-VLP were identified. Fusion proteins of BPV6-L1 and EGFP as a model foreign protein were constructed and produced. Only the fusion protein in which EGFP was inserted between amino acids 136 and 137 of BPV6-L1 self-assembled into VLPs and did not exhibit hindrance of the conformation of EGFP. Chimeric BPV6-VLP-immunized mice produced specific IgG against both BPV6 and EGFP. This is the first demonstration of the production of an immunogenic, bivalent, chimeric BPV6-VLP incorporating an entire protein for stable surface display. Thus, immunogenic chimeric BPV6-VLP may constitute a promising vaccine platform.

摘要

病毒样颗粒(VLPs)被认为是疫苗开发的有用工具,因为它们能诱导免疫反应且安全。此外,VLPs 可用作展示外源抗原以引发免疫反应的平台。在本研究中,我们旨在生产一种嵌合 VLP,该 VLP 由牛乳头瘤病毒 6 型(BPV6)的 L1 蛋白组成,可在其表面展示完整的外源蛋白。基于对 BPV6-VLP 构象结构的预测,确定了候选插入位点,用于将外源蛋白插入 BPV6-VLP。构建并生产了 BPV6-L1 和 EGFP 融合蛋白作为模型外源蛋白。只有将 EGFP 插入 BPV6-L1 的氨基酸 136 和 137 之间的融合蛋白才能自组装成 VLPs,并且 EGFP 的构象不受阻碍。用嵌合 BPV6-VLP 免疫的小鼠产生了针对 BPV6 和 EGFP 的特异性 IgG。这首次证明了能够稳定表面展示完整蛋白的免疫原性、二价嵌合 BPV6-VLP 的生产。因此,免疫原性嵌合 BPV6-VLP 可能构成有前途的疫苗平台。

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