Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines.
Sherry L., Bahar MW., Porta C., Fox H., Grehan K., Nasta V., Duyvesteyn HME., De Colibus L., Marsian J., Murdoch I., Ponndorf D., Kim S-R., Shah S., Carlyle S., Swanson JJ., Matthews S., Nicol C., Lomonossoff GP., Macadam AJ., Fry EE., Stuart DI., Stonehouse NJ., Rowlands DJ.
Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900's, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.