FOR UK farmers, it is the worst nightmare: a return of the foot and mouth disease that in 2001 devastated the nation’s agriculture. Added to this is the bitter realisation that the virus must have escaped from one of two premier laboratory facilities for combating the disease.
The incident has rekindled questions about the safety of existing vaccines against foot and mouth, which are made from killed viruses. In addition to the possibility of viruses escaping during manufacture, there is a risk of failing to kill all the viruses in a batch. There are, however, new “synthetic” vaccines under development, which might overcome these disadvantages.
As Â鶹´«Ă˝ went to press, an official investigation into the source of the virus, which infected cows in Surrey, southern England, was still under way. But the strain of the virus, 01/BFS67, indicates that it must have come from either the Institute for Animal Health (IAH), the world’s leading reference laboratory for diagnosing and monitoring foot and mouth disease, or the firm Merial Animal Health, which used the strain to make vaccines. The 01/BFS67 strain has not circulated in European animals for 40 years. Both the IAH and Merial are based at Pirbright, just 5 kilometres from the site of the first case.
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Vaccine production is known to be risky. Almost all foot and mouth outbreaks in western Europe in the 1980s resulted from failure of the chemical formaldehyde to kill the virus in vaccine batches.
“Almost all foot and mouth outbreaks in western Europe in the 1980s resulted from failure to kill the virus in vaccines”
Nowadays other chemicals, such as binary ethyleneimine or beta propiolactone, are used, but these are not foolproof. “The foot and mouth virus can clump, so the chemicals kill the viruses around the edge of the clump but spare the ones in the middle,” says John Oxford, a virologist at St Bartholomew’s Hospital in London. “If the inactivant doesn’t do its job, you can still have live virus in the vaccine.”
Vaccines under development would avoid these problems. One, pioneered by Marvin Grubman and colleagues at the US Department of Agriculture’s Animal Disease Center on Plum Island, New York, includes only protein fragments from the foot and mouth virus. Developed in collaboration with GenVec, a firm in Gaithersburg, Maryland, genes for viral peptides are injected into animals inside a harmless adenovirus that cannot reproduce and so poses no threat. “We’ve tested it at Plum Island on cattle, and so far it’s looking promising,” says Grubman.
Equally important, says Grubman, is the fact that it is possible to distinguish infected from vaccinated animals, as infected animals will have antibodies to viral proteins not included in the vaccine. This overcomes one of the key objections to using vaccines in countries free of foot and mouth disease – that infected and vaccinated animals produce the same antibodies and so are indistinguishable, possibly leading to missed cases of the disease.
It will be years before the vaccine is ready, according to Grubman. “We’ve only tested it so far in the lab, so we don’t have evidence from the field yet in a controlled trial,” he says.
Much closer to realisation is a synthetic vaccine being developed by United Biomedical of Hauppauge, New York, although the prototype vaccine is aimed mainly at pigs and has not yet been optimised for cattle.
Composed of a short peptide matching one found on the surface of the foot and mouth virus, the vaccine has already been tested successfully in pigs and approved by the government of China, where the disease is common in swine. This year, the company completed construction of a manufacturing facility in Shanghai. “It’s the first synthetic, peptide-based vaccine for swine foot and mouth,” says company chairman Chang Yi Wang.
As Â鶹´«Ă˝ went to press, emergency containment measures implemented by British government veterinarians appeared to be holding. Only one additional cow, at a nearby farm, had tested positive for the virus, which in cattle causes sores and blisters in the mouth and on the hooves.
The UK government has not yet decided whether to vaccinate animals to prevent further spread of the disease. However, Merial is now making 300,000 doses of vaccine, which might be given to cattle if the epidemic spreads.
In 2001, between 6.5 and 10 million animals in the UK were slaughtered to bring the most recent epidemic under control, at a cost of some ÂŁ8.5 billion.
