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

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

NPJ vaccines (2021-01-10)
Mohammad W Bahar, Claudine Porta, Helen Fox, Andrew J Macadam, Elizabeth E Fry, David I Stuart
ANOTACE

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.

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Sigma-Aldrich
Dulbecco′s Phosphate Buffered Saline, With MgCl2 and CaCl2, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Anti-Poliovirus Blend Antibody, clones 583-G8-G2-A4, 591-B1-H7-D1, and 613-F1-B5-E5, ascites fluid, Chemicon®, from mouse