'Holy grail' of foot-and-mouth vaccines developed

A group of scientists have developed a new type of vaccine to combat food-and-mouth disease which contributed to the deaths of over 7 million livestock and is estimated to have cost the economy £2bn.

Globally it remains one of the most economically important diseases in livestock worldwide, with approximately 3 to 4 billion doses of vaccine administered every year.

The new vaccine is 'safer to produce, more stable and easier to transport' according to scientists from the University of Oxford and the Pirbright Institute.

"What we have achieved here is close to the holy grail of foot-and-mouth vaccines. Unlike the traditional vaccines, there is no chance that the empty shell vaccine could revert to an infectious form," said Professor Dave Stuart, one of the leaders of the study from Diamond Light Source and Oxford University.

"Instead of using infectious virus as the basis for the vaccine, which is the main traditional method of vaccine development, the team synthetically created empty protein shells to imitate the protein coat that forms the strong outer layer of the virus.

"By using Diamond’s visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, we were able to visualise something a billion times smaller than a pinhead. This allowed us to further enhance the design of the empty shells atom by atom. Through information gained at Diamond, we could verify that these have essentially the same structure as the native virus to ensure an appropriate immune response."

Early clinical trials of the new vaccine in cattle have shown it is as effective as current vaccines. Whilst a commercial product is still several years away, the team hopes that the technology can be transferred as quickly as possible to make it available to a global market.

One of the problems of existing vaccines against foot and mouth disease is identifying which animals have been vaccinated and which haven't.

They have used a new method to produce a vaccine that doesn't rely on inactivating the live, infectious virus which causes the disease – and is therefore much safer to produce.

Instead the vaccine consists of empty virus shells that have been produced synthetically, and are designed to produce an immune response that protects against the disease.

Furthermore, the empty shells have been engineered to be more stable, making the vaccine much easier to store because the need for the vaccine to be refrigerated is reduced.

The 2001 foot and mouth outbreak in Britain was devastating and cost the economy billions of pounds in control measures and compensation. One recommendation in a Royal Society report following the epidemic recommended the development of new approaches to control the virus.

Foot and mouth disease is endemic in central Africa and some parts of the Middle East and Asia.

The traditional FMDV vaccine has to be produced and stored in a chilled and stable environment, making distribution in these areas problematic.

Preclinical trials on the new synthetic vaccine have shown it to be stable at temperatures up to 56°C for at least two hours, making transporting and storing the vaccine much easier. Not only that, the vaccine does not require high containment, making it safer and cheaper to produce.

Dr Bryan Charleston leads a team at The Pirbright Institute in the UK which has developed a detailed understanding of the immune response to FMDV in cattle and is leading the vaccination trials work. He says, "The ability to produce a vaccine outside of high containment and that does not require a cold storage chain should greatly increase production capacity and reduce costs. Globally there is an undersupply of the vaccine due to the high cost of production and this new development could solve this problem and significantly control foot-and-mouth disease worldwide."

The breakthrough is the result of a major collaborative project spanning over 20 years.

The team synthetically created empty protein shells using a methodology developed by Professor Ian Jones from the University of Reading.

The structure of FMDV was first solved by Dave Stuart at Diamond’s predecessor, the SRS at Daresbury, back in 1989. Diamond was used to develop structure-based methods for predicting stabilising mutations tailored to each serotype (variations of the virus).

Virus crystals are very small and fragile, making them difficult to study. Gwyndaf Evans, principal beamline scientist on I24 says, "On I24 we are able to study the crystals at room temperature, which means we don’t have to physically handle them, thereby preserving their intrinsic high quality. However, because the crystals are so tiny and weakly diffracting, we need a microfocus beam and high X-ray intensity. This combination is what makes I24 unique, there is nowhere else in the world with this capability at the moment."

The research at the Pirbright Institute was the direct result of funds allocated in the wake of the 2001 outbreak.

Incorporation of the mutations into the empty shells, validation of the predicted improved stability and showing they stimulate protective immunity was performed by Dr Bryan Charleston at Pirbright Institute and Prof. Ian Jones at Reading University and their teams.

The stable mutated empty shells were analysed by the Oxford team to demonstrate they remain as authentic copies of the original viruses. Together the three groups have developed a system for the production of empty protein shells at commercially viable amounts.

"I think what the collaboration have achieved here is amazing. This is a great example of Diamond playing a crucial role in providing a solution to a problem of global significance. It should be able to get to market and really start to improve animal health on a global scale."

Nigel Gibbens, the UK's Chief Veterinary Officer, comments: "There are many more years of work and research to be done to get this vaccine ready for use, but this is undoubtedly an exciting leap forward. Once available, vaccines of this type would have clear advantages over current technology as a possible option to help control the disease should we ever have another foot and mouth disease outbreak.

"This vaccine has been developed using some truly groundbreaking techniques which are a credit to the quality of British scientists working in the field of animal health."