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TitleMammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.
Journal, issue, pagesNPJ Vaccines, Vol. 6, Issue 1, Page 5, Year 2021
Publish dateJan 8, 2021
AuthorsMohammad W Bahar / Claudine Porta / Helen Fox / Andrew J Macadam / Elizabeth E Fry / David I Stuart /
PubMed AbstractGlobal 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 ...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.
External linksNPJ Vaccines / PubMed:33420068 / PubMed Central
MethodsEM (single particle)
Resolution3.0 Å
Structure data

11106

6z6w

EMDB-11106, PDB-6z6w:
Poliovirus type 3 (strain Saukett) stabilised virus-like particle (PV3 SC8) from a mammalian expression system.
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-SPH:
SPHINGOSINE

Source
  • human poliovirus 3
KeywordsVIRUS LIKE PARTICLE / Capsid protein

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