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植物源3型脊髓灰质炎稳定病毒样颗粒——一种候选合成脊髓灰质炎疫苗。

Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

作者信息

Marsian Johanna, Fox Helen, Bahar Mohammad W, Kotecha Abhay, Fry Elizabeth E, Stuart David I, Macadam Andrew J, Rowlands David J, Lomonossoff George P

机构信息

John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

The National Institute for Biological Standards and Control, Potters Bar, EN6 3QG, UK.

出版信息

Nat Commun. 2017 Aug 15;8(1):245. doi: 10.1038/s41467-017-00090-w.

Abstract

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.Despite the success of current vaccination against poliomyelitis, safe, cheap and effective vaccines remain sought for continuing eradication effort. Here the authors use plants to express stabilized virus-like particles of type 3 poliovirus that can induce a protective immune response in mice transgenic for the human poliovirus receptor.

摘要

脊髓灰质炎病毒(PV)是脊髓灰质炎的病原体,脊髓灰质炎是一种自古以来就为人所知的使人致残的疾病。PV有两种不同的抗原形式,D型和C型,其中只有D型能引发强烈的中和反应。开发一种具有D抗原性、没有现有疫苗缺点的基于合成稳定化病毒样颗粒(sVLP)的疫苗,将是朝着最终根除脊髓灰质炎病毒迈出的重要一步。这样的sVLP将保留原始病毒颗粒的天然抗原构象和重复结构,但缺乏感染性基因组物质。在本研究中,我们报告了在植物中合成稳定化的PV病毒样颗粒的生产。携带人PV受体基因的小鼠在用植物制造的PV sVLP免疫后可免受野生型PV感染。通过冷冻电子显微镜和单颗粒重建以3.6 Å分辨率对稳定化突变体进行的结构分析揭示了一种与野生型PV3几乎无法区分的结构。尽管目前针对脊髓灰质炎的疫苗接种取得了成功,但仍在寻求安全、廉价且有效的疫苗以继续开展根除工作。在此,作者利用植物表达3型脊髓灰质炎病毒的稳定化病毒样颗粒,该颗粒可在人脊髓灰质炎病毒受体转基因小鼠中诱导保护性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a19/5557999/a0b125842c68/41467_2017_90_Fig1_HTML.jpg

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