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

DOI: 10.1038/s41467-017-00090-w DOI Help

Authors: Johanna Marsian (John Innes Centre) , Helen Fox (The National Institute for Biological Standards and Control) , Mohammad W. Bahar (University of Oxford) , Abhay Kotecha (University of Oxford) , Elizabeth E. Fry (University of Oxford) , David I. Stuart (Diamond Light Source; University of Oxford) , Andrew J. Macadam (The National Institute for Biological Standards and Control) , David J. Rowlands (University of Leeds) , George P. Lomonossoff (John Innes Centre)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 8

State: Published (Approved)
Published: August 2017

Open Access Open Access

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.

Journal Keywords: Biotechnology; Expression systems; Vaccines; Virus structures

Diamond Keywords: Viruses; Poliomyelitis

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 15/08/2017 10:26


Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)