4.8 Article

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

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NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00090-w

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资金

  1. UK Biotechnological and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Grant Understanding and Exploiting Plant and Microbial Secondary Metabolism [BB/J004596/1]
  2. John Innes Foundation
  3. Wellcome Trust core award [090532/Z/07/Z]
  4. Wellcome Trust JIF award [060208/Z/00/Z]
  5. Wellcome Trust equipment grant [093305/Z/10/Z]
  6. Wellcome Trust
  7. MRC [MR/N00065X/1]
  8. BBSRC
  9. WHO/Gates foundation award [RG.IMCB.I8-TSA-083]
  10. Jenner Investigator
  11. WHO
  12. BBSRC [BBS/E/J/000PR9794] Funding Source: UKRI
  13. Biotechnology and Biological Sciences Research Council [BBS/E/J/00000166, BBS/E/J/000PR9794] Funding Source: researchfish

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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 angstrom resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.

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