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

机译:植物制造的3型脊髓灰质炎稳定VLPs-候选合成脊髓灰质炎疫苗。

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摘要

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.
机译:脊髓灰质炎病毒(PV)是脊髓灰质炎的病原体,脊髓灰质炎是上古以来已知的一种严重的人类疾病。 PV以两种不同的抗原形式D和C出现,其中只有D形式会引发强烈的中和反应。开发具有D抗原性的合成生产的稳定化的基于病毒样颗粒(sVLP)的疫苗,而没有当前疫苗的缺点,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将保留天然的抗原构象和原始病毒颗粒的重复结构,但是缺乏传染性基因组物质。在这项研究中,我们报告了植物中合成稳定的PV VLP的生产。携带人PV受体基因的小鼠在用植物制成的PV sVLP免疫后,可免受野生型PV侵害。通过冷冻电子显微镜和单粒子重建对3.6Å分辨率的稳定突变体进行结构分析,发现其结构与野生型PV3几乎没有区别。尽管目前针对脊髓灰质炎的疫苗接种成功,但仍在寻求安全,廉价和有效的疫苗以继续根除努力。在这里,作者使用植物表达稳定的3型脊髓灰质炎病毒样颗粒,该颗粒可在转染了人类脊髓灰质炎病毒受体的小鼠中诱导保护性免疫应答。

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