Genetic manipulation method could bypass the need to grow live poliovirus

Work at NIBSC has led to a new method to produce a stable replica of poliovirus that could enable safer production of vaccines, and has just been published in PLOS Pathogens.

Polio is almost completely eradicated, but polio vaccines are still needed to protect against the possibility of re-emergence. However, existing vaccine production methods require growing live viruses, and this poses safety risks.

Previous research suggested that the empty protein shell of poliovirus, devoid of any genetic material, has the potential to serve as an effective vaccine, and it can be produced without growing live viruses. However, these shell particles were too unstable to be practical for use as vaccines. Helen Fox and colleagues at NIBSC have developed a new method to produce polio protein shells that are stable enough to consider using as vaccines.

To develop the stable particles, the researchers first identified mutations in the three types of poliovirus which increased shell stabilitywithout altering the structures of the shells. By systematically introducing combinations of these new mutations into viruses, the scientists increased shell stability to a level compatible with vaccine production. When tested in mice and rats, the particles caused the animals to generate high levels of protective antibodies, suggesting that they could function effectively as vaccines. What’s more, these particles can be stored without refrigeration for many months without significant loss of activity.

The lead scientist at NIBSC, Dr. Andrew Macadam, said:

“The approach we developed was remarkably effective and worked for all three types of polio so may have applications in the design of vaccines against other virus diseases. The challenge now is to transfer these designs to production systems that can deliver large quantities cheaply so that a vaccine for global use is feasible.”

This work is part of a WHO-funded consortium involving experts at the Universities of Leeds, Oxford and Reading, the John Innes Centre and the Pirbright Institute. Work within the Consortium is ongoing to develop a viable production system for these empty shells and determine their structures as well as investigating other means of stabilizing the shells. Clinical studies would be required to establish whether they might eventually replace existing polio vaccines.