Breakthrough in next-generation polio vaccines

Researchers have taken a major step towards producing a more affordable and lower-risk polio vaccine using virus-like particles (VLPs). These particles mimic the outer protein shell of poliovirus, but are empty inside. This means there is no risk of infection, but the VLP still causes the immune system to respond.

Now, a research project led by Professor David Rowlands, Emeritus Professor of Molecular Virology at the University of Leeds, has tested the effectiveness of using different yeast, insect, mammalian and plant cells as expression systems to generate VLPs.

In a paper published in Nature Communications, the findings show that VLPs produced in both yeast and insect cells can perform equally or better than the current inactivated polio vaccine (IPV), which creates an immune system response by using a killed version of the poliovirus.

Professor Nicola Stonehouse is Chair in Molecular Biology at the University of Leeds School of Molecular and Cellular Biology and one of the senior authors on the paper. Professor Stonehouse said: "Any vaccine is only as effective as the number of children that it reaches. The key is to make vaccines universally accessible, as all children have a right to be protected from diseases such as polio, no matter where they live. Ultimately, VLPs would significantly contribute to vaccine equity.

"Thanks to research like this, we are already working with commercial partners to produce the next generation of polio vaccines. Although we don't yet know when these will be widely available, we are getting much closer to a polio-free future."

Today's polio vaccines

Currently, IPV is relatively expensive to produce because it requires high levels of bio-containment to minimise the risk of leaks of live poliovirus, which could result in outbreaks. VLPs are non-infectious and would not need to be handled under such stringent bio-safety conditions.

Oral polio vaccine (OPV), which contains live but weakened vaccine-virus, is also used in vaccination against polio.

Future polio vaccines

However, once all remaining strains of wild poliovirus have been successfully eradicated, OPV use will need to stop to eliminate a small risk of circulating variant poliovirus that can be associated with its use.

In populations where large numbers of people are unvaccinated and sewage disposal is poor, such strains can cause an outbreak through contact with faeces, often via contaminated water.

At this time, IPV will be the only polio vaccine available to populations, but expensive manufacturing procedures make it unaffordable for lower-income countries.

Non-infectious VLPs are easier to produce than current IPVs and the research has shown they are more temperature stable, thanks to genetic alteration of the outer shell. As they are non-infectious, this means they will be less expensive to produce, helping to improve equitable access to vaccination.

Dr. Martin Eisenhawer is the WHO focal point for the development of Polio VLPs and the VLP consortium led by the University of Leeds. Dr. Eisenhawer said: "The WHO, when looking at research and development priorities for new generation Polio vaccines, has early on identified VLPs as a technology that could be an ideal tool especially for the post-eradication period with the aim for Polio VLPs to be ultimately produced as a very cost effective and safe vaccine by developing country manufacturers for the benefit of a global supply.

"Through an extensive collaboration with the research consortium, vaccine manufacturers and the Global Polio Eradication Initiative (GPEI), we are approaching this goal with the new developments. This research shows that a critical new polio vaccine solution is on the horizon. It would be a critical new tool to not only achieve but sustain global polio eradication, and ensure -- in an equitable way -- that no child anywhere will ever again be paralysed by any poliovirus. It is about ensuring that once polio is eradicated, it will stay eradicated."

The international research collaboration, which was funded by the World Health Organization, also included researchers from the University of Oxford, the Medicines and Healthcare products Regulatory Agency (MHRA), the John Innes Centre, The Pirbright Institute, the University of Florida and the University of Reading. The structural data was collected using a cryo-electron microscope at Diamond Light Source.

VLPs are already used in vaccines for hepatitis B and human papillomavirus (HPV) -- and researchers have been working for over a decade to apply this successful technology to help eradicate polio.

The next generation of polio vaccinations are likely to be produced in yeast or insect cells, as the research showed these were effective when tested on rats and mice. These cell expression systems are also favoured by companies and are used for existing vaccinations, due to their low cost.

Dr Lee Sherry was one of four lead authors on the paper while working at the University of Leeds. Dr Sherry, who now holds a position at the University of Glasgow, said: "Following the success of using VLP vaccines in preventing hepatitis B and HPV-related diseases, it is very exciting to see this research being taken forward by industrial partners as a safer vaccine production strategy as we move towards a polio-free world."