PIRBRIGHT INSTITUTE

Virologists have devised a way to create an entirely synthetic vaccine for foot-and-mouth disease. The vaccine could prevent future outbreaks of the disease, and potentially lead to new treatments for polio and other human diseases.

Bryan Charleston, head of the Livestock Viral Diseases Programme at the Pirbright Institute in Woking, UK, and his colleagues used computer simulations to create a model of the protein shell of the virus that causes the disease, then reconstructed it from synthetic protein components. The synthetic shell contains no genetic material, and so it cannot infect the animals. But it will spur the immune system to produce antibodies that would protect them from the real virus.

In 2001, an outbreak of foot-and-mouth disease in the United Kingdom led to the destruction of nearly 10 million animals. It cost the economy an estimated £8.5 billion (US$12.9 billion) in agricultural and tourism costs, and spurred a decision to protect against future outbreaks with vaccination rather than mass slaughter.

In 2007, however a vaccine made from inactivated virus caused another UK outbreak. The authors say that there is absolutely no chance that their new vaccine could revert into an infectious virus because it contains no viral genes. Also, being entirely synthetic, it cannot be contaminated with live virus during manufacturing.

It will be 6–8 years before the vaccine is available to farmers, they estimate.

But if the method used to create the vaccine proves successful when scaled to commercial production, it could also be used to create vaccines for human diseases that are caused by viruses of the same family, such as hand, foot and mouth disease, which is ubiquitous in Southeast Asia, and polio, which still blights the lives of millions of people in the developing world.

“Viruses are all very different from each other, and each will come with its own set of problems to solve,” says co-author David Stuart, a structural biologist at the University of Oxford, UK, who is working with the World Health Organization and the Gates Foundation to apply the techniques to the eradication of polio. ”But if we could use this to move away from inactivated polio viruses in the vaccines, it would have very powerful impacts because we are so close to ending this disease.”

JEFF J MITCHELL/REUTERS

Solving geometry

Earlier attempts to produce a synthetic vaccine for foot and mouth disease were often thwarted by peculiarities of viral geometry. Both the polio and foot-and-mouth viruses are shaped as an icosahedron — a polyhedron with 20 triangular faces. “When those are clipped together, it’s the edges that are the weak spots,” explains Charleston. The synthetic protein shells simply fall apart during transport and dissemination, rendering the product useless.

The team got around the problem by engineering the vaccine to have disulphide bonds cross-linking the protein triangles together. This makes the structure more stable, which means it will not require cold storage and that it will be cheaper to produce and distribute. The results are published in PLoS Pathogens1.

It is this innovation that is particularly important and is what makes this paper “a huge step forward”, says John Oxford, a virologist at St Bartholomew’s and the Royal London Hospital. “This really is an ace paper — they've truly given the entire issue a whole new dimension,” he says.

Oxford agrees with Stuart and Charleston that the new vaccine is unable to cause an infection or outbreak.

Marvin Grubman, an animal-disease researcher at the US Department of Agriculture in Orient Point, New York, says that the new vaccine “is a good piece of work, but certainly not very novel”, pointing to a foot-and-mouth vaccine his team devised that uses adenovirus to deliver empty viral shells. That vaccine, he says, has been approved for use in the United States for cases of emergency.

The authors however point out that their vaccine does not require the injection of live viruses and that it would be suitable for preventive vaccination as well as in cases of severe outbreaks.