NICE, France _ A single poster among the more than 200highlighted _ perhaps unwittingly _ the 115-year continuumbetween Louis Pasteur's life-saving rabies vaccine, which madehistory in 1880, and France's genetically engineered campaignagainst the wild foxes and free-roaming dogs that carry the lethalvirus today.

Because such animals are inaccessible to injected vaccines,helicopters every two months strew pellets containing recombinantattenuated viruses over areas populated by the animals. These ediblevaccines, explained veterinary virologist Carolin Schumacher, whoprepared the poster, incorporate a bait that is irresistible to foxes.

"The fox is a curious animal," she told BioWorld. "He isattracted to these inch-wide blister-packed discs by their unfamiliarodor and shape. The fox plays with the pellet as if it were chewinggum, then swallows its vaccine contents."

What the animal ingests is a whole rabies virion in which the geneencoding highly virulent arginine amino acid has had its triplet codonremodeled to yield a benign lysine moiety. The resulting rabiesglycoprotein, Schumacher said, "is a pathogenic in mice even wheninjected into their brains in high concentration."

A single dose then protected nine out of nine foxes challenged withwild-type virus after receiving the vaccine, while nine of 10 controlanimals died, according to unpublished data.

Schumacher is the rabies research project manager at Virbac SA, avaccine-development company near Nice. She said that the originalrabies SAG-Dufferin strain was derived in 1935 from a victim inAlabama, presumably named Dufferin.

France's airborne blitz to bomb fox habitats with the recombinantpellets began in 1989, with 2 million baits, averaging 13 per squarekilometer, dropped twice a year. The first year saw a decrease inrabid animals of 51 percent; in 1991, 81 percent; in 1992, 90 percent.

Even in million-dose batches, Schumacher observed, "the baits arequite expensive, about 4.5 to 5 francs each."

The campaign, in cooperation with some neighboring countries, mustcontinue indefinitely, Schumacher pointed out, because the massivereservoir of rabid foxes in Russia moves steadily westward throughPoland, Germany France, Austria and Switzerland.

From Vulpine Targets To Canine

In Tunisia the problem is not wild foxes but half-wild rabies-pronedogs. Virbac is producing a differently engineered edibleimmunogen, more suitable for use in human habitats. Its amino-acidalteration was designed by the Institute for Virus Genetics at France'sNational Center for Scientific Research, as was the vulpine version.

It protected three of four dogs in preliminary trials. Unlike the liquidblister pack that tantalizes the foxy population, the canine baitcontains a freeze-dried solid dose. It achieved 81.4 percent to 100percent acceptance among trial dogs, 34 percent of whom were feral.

Tunisia's health authorities will decide in July whether to undertakeVirbac's canine vaccination program.

Belgium a decade ago was the first country to drop Frenchexperimental rabies bait on a restricted fox habitat. Its success led toFrance's ongoing campaign.

Belgian immunologist Paul-Pierre Pastoret defended the use ofstrewn-bait vaccine to control the spread of rabies in the wild. Muchpublic opinion in Europe, notably in Germany, opposes this strategyas dangerous. So far, the German authorities will have none of it, hesaid.

To underline the vaccine's risk factor, Pastoret, who headsimmunology and vaccinology at the University of Liege, declared: "If1,000 vaccinated dogs a year were imported into Britain, a singlecase of human rabies might occur in 1,250 years." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.