Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines

Abstract

While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.

Author Summary

There is a need for safe production of polio vaccines as eradication is approached. Empty capsids in a native conformation are produced by poliovirus and other picornaviruses seemingly as a necessary part of the assembly process, possibly to provide a reservoir of subunits in a form that is resistant to cellular pathways that target unfolded or hydrophobic motifs for proteolytic degradation. Normally they are not very stable prior to genome encapsidation but more stable forms, if they existed, could potentially be useful as vaccines. Genetic variants that increase empty capsid stability have been identified and by artificially combining several in one sequence the evolutionary constraints have been bypassed, with the resulting stable empty capsids representing essentially dead-end products. They induce antibody efficiently and are stable on storage. Empty capsids can be produced by recombinant expression which, if it were efficient enough, could provide a source of immunogenic particles suitable for use as vaccines without the need for live virus at any stage of production. This would be ideal for a post-eradication world.