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Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines

DOI: 10.1038/s41541-020-00267-3 DOI Help

Authors: Mohammad W. Bahar (University of Oxford) , Claudine Porta (University of Oxford; The Pirbright Institute) , Helen Fox (The National Institute for Biological Standards and Control) , Andrew J. Macadam (The National Institute for Biological Standards and Control) , Elizabeth E. Fry (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Npj Vaccines , VOL 6

State: Published (Approved)
Published: January 2021

Open Access Open Access

Abstract: Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.

Journal Keywords: Vaccines; Virology

Diamond Keywords: Viruses; Poliomyelitis

Subject Areas: Biology and Bio-materials, Medicine

Technical Areas:

Added On: 11/01/2021 10:09

Discipline Tags:

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

Technical Tags: