Vaccine from Rabid Rabbits

by Food and Drug Administration (FDA)

(Page 3 of 3)

A small dog raced wildly along the sidewalk, a black and white blur among children on their way to school. It stopped only for an instant — just long enough to bite a boy on the ankle — and then was gone.

Hours later the boy couldn't be sure that the dead dog he was shown at the county health department was the one that had bitten him. Rabid dogs had been reported in the county, and they were known to attack without provocation. Tests would show later that the dog did indeed have rabies. But even before they knew the test results, county health authorities and the boy's parents agreed he had to start the Pasteur treatment, a course of injections to protect against a disease that would otherwise almost certainly be fatal.

That all happened more than 40 years ago. Back then — and, in fact, since 1885, when French scientist Louis Pasteur successfully used his rabies treatment in a human patient — postexposure rabies immunization consisted of 23 or more doses of a vaccine made from spinal cords of rabbits injected with the rabies virus. Pasteur and his co-workers had discovered that rabid rabbit tissue lost infectivity after exposure to room air for 15 days. Yet injection of this rabbit brain material protected animals challenged with lethal doses of rabies virus. They had in effect produced the first rabies vaccine.

In one of history's most celebrated clinical trials, Pasteur treated a 9-year-old boy who had been savagely bitten by a dog judged to be rabid on the basis of erratic and unusual behavior before its death. One piece of "evidence" for the diagnosis of rabies: The dog's stomach was full of "hay, straw, and fragments of wood." Today that would hardly be accepted as proof that the animal had rabies, but it was enough to convince Pasteur that, without treatment, the boy would certainly die.

Young Joseph Meister didn't die of rabies, and we will never know whether he was even exposed to the disease. But we do know that the Pasteur treatment Meister and thousands of others received was a risky procedure justified only by the knowledge that untreated rabies was invariably fatal.

The old Pasteur vaccine and others like it contained "fixed virus" — live rabies virus that had been stabilized by injecting and recovering it from a series of laboratory animals — and animal brain tissue. Injected into humans, this type of vaccine could cause serious, even fatal, reactions, including a form of paralysis that advanced from the legs and arms to the muscles of the face and throat. Paralytic vaccine accidents occurred in about 1 in every 1,600 patients receiving the Pasteur treatment, 30 percent of whom died.

Over the decades, scientists improved both the safety and effectiveness of rabies vaccines. A vaccine produced from duck embryos, approved for marketing in the United States in 1956 and used over the following 16 years, cut the paralytic accident rate to 1 in 32,000. A substantially different vaccine licensed in 1980 and in use today has been associated with so few cases of paralytic disease — only 3 in the first 500,000 patients — that it is not certain the vaccine actually caused the paralysis. Sore arm, malaise, headache, and other mild symptoms occur fairly often, however. In one study, 21 percent of patients had local reactions. Allergic symptoms are far less common, about 1 in 10,000 cases, and none has been fatal.

Today's rabies vaccines are the product of advances in virology and immunology, and in the science of tissue culture — growing cells in the laboratory. One product is made by allowing the rabies virus to multiply in cultures of human diploid cells, cells that contain two complete sets of human chromosomes. The other licensed vaccine is made using fetal rhesus monkey cells. The viruses harvested from these human or monkey cell cultures are chemically killed, but the vaccines produced are nonetheless immunologically very potent. Instead of 23, 28, and sometimes as many as 40 injections of the old Pasteur-type vaccine, only five injections of modern rabies vaccines administered over 28 days afford full protection. (Booster shots are administered if a person is suspected of having had another exposure to rabies.)

Although he didn't have the benefit of modern vaccine technology, the boy bitten on his way to school 40-odd years ago suffered nothing more serious than a bad scare and sore arms. Much the same awaits anyone treated today for exposure to rabies. But today, for the first time since Pasteur, the treatment is no longer a calculated risk.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.