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- Title
Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.
- Authors
Bahar, Mohammad W.; Porta, Claudine; Fox, Helen; Macadam, Andrew J.; Fry, Elizabeth E.; Stuart, David I.
- 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.
- Subjects
POLIOMYELITIS vaccines; POLIOVIRUS; OPEN reading frames (Genetics); SEROTYPES; ELECTRON microscopy
- Publication
NPJ Vaccines, 2021, Vol 6, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-020-00267-3