Microbe of the Month: A malevolent beast outfoxed: Genetic engineering could be the means of at last ridding Europe of rabies, says Bernard Dixon

MEMBER states of the European Community are about to fail to meet another deadline. They are supposed to have eliminated the rabies virus from the wildlife in their countries by the end of the year, but pockets of infection remain.

The turmoil in Eastern Europe has not helped; for instance, collaboration between Italy and the former Yugoslavia in exterminating rabies from their borderlands has all but broken down. It seems, therefore, that the precautions, including quarantine, that have kept Britain virtually free of rabies since the First World War will need to remain in force a little longer.

The eradication campaign now rests in part on a genetically engineered vaccine that has been successful in eliminating the virus from foxes in a large part of Belgium. Alarmists may associate genetic engineering with unspeakable horrors, but it is on the verge of clearing from an entire continent one of humankind's most loathsome infections.

The rabies virus is a lethal and malevolent microbe. In one recent case, a man in Texas was bitten on the right index finger by a bat. More than a month later, his hand became weak and he sought medical attention. Six days of increasing pain and torment followed.

Before he slipped into a coma and died, the man suffered hallucinations and high fever, continuous drooling, frequent spasms in the face, mouth and neck, severe breathlessness and difficulty in swallowing.

Although humans can be protected by a series of injections, even after being bitten by a rabid animal, the inoculations are expensive and can have side-effects. And many people are immunised unnecessarily, not knowing whether the animal concerned was in fact carrying the disease.

The main eradication effort in Europe is focused on foxes. The first strategy was to cull them, but measures such as gassing, poisoning and trapping only partially achieved the target.

The alternative approach has been immunisation. An injectible vaccine, of the sort used to protect domestic animals, is hardly practical. Researchers therefore developed weakened strains of the rabies virus that, when taken by mouth, trigger disease-fighting antibodies, without causing the disease itself.

Baits carrying these vaccines were used first in Switzerland, then in France and Germany.

However, two worries have emerged: these live, attenuated viruses retain some degree of virulence towards rodents; and they could, in theory, regain their virulence against foxes and other animals.

This prompted researchers at Transgene SA, in Strasbourg; Rhone Merieux, in Lyon; and the University of Liege to investigate the feasibility of a genetically engineered vaccine lacking such drawbacks. Instead of trying to modify the virus, the genetic engineers harnessed only the part of it that induces the protective antibodies and cannot cause the disease. They selected one component of the virus's protein coat and transferred the gene - a unit of hereditary material - responsible for producing this protein into vaccinia, the virus formerly used to immunise us against smallpox.

The hope was that this hybrid virus would grow in the cells of the fox, making the rabies protein and thereby provoking the animal to make antibodies against the disease.

It worked well. After helicopters had dropped 25,000 baits carrying the vaccine over a 2,200sq km area of southern Belgium, 81 per cent of foxes later sampled had become immune to rabies. And as predicted from a model of the percentage immunity required to block transmission of the virus, the disease disappeared accordingly.

The continental rabies epidemic that necessitated the familiar posters and quarantine measures at British ports began in Poland during the Second World War. Now, thanks to the new vaccines, what once appeared to be an inexorable movement towards the coast of France has been arrested, and the UK and Ireland may soon be free of this hideous threat from across the Channel.

(Photograph omitted)

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