Made-to-Order Vaccines

By Claudia Wallis

Preventing herpes and other ills by scrambling DNA

The immediate targets are herpes, hepatitis and influenza, but the potential is much greater. Last week a group of scientists with the New York State department of health announced an exciting and imaginative application of the genetic-engineering techniques that are transforming modern medicine. Using the sophisticated new cut-and-paste methods of manipulating genes, the researchers were able to transform ordinary smallpox vaccine into vaccines that may be able to prevent the other three diseases. So far the results have been tested in animals only, but Virologist Enzo Paoletti, a senior scientist on the project, is confident that they will work in humans as well. What is more, Paoletti's Albany-based team has already begun work on a version for malaria, the No. 1 infectious health threat in the world. Says Paoletti: "We see no reason why our approach won't work with virtually any infectious disease, whether it is viral, bacterial or even parasitic in nature." Though some scientists have reservations about the techniques, a senior official of the usually restrained World Health Organization declares, "This is a scientific achievement of the first order."

The starting point for the dramatic research is the oldest vaccine on earth: a smallpox prophylactic made from a live cowpox virus called vaccinia. It was developed two centuries ago by Edward Jenner, a British physician who had observed that milkmaids exposed to cowpox were immune to smallpox. Because vaccinia is an unusually large virus and because it has been familiar to scientists for so long, it was an ideal subject for genetic tinkering.

What Paoletti and his colleague, Virologist Dennis Panicali, set out to do was to alter the genetic material, or DNA, of cowpox virus by inserting a gene from another virus--herpes, hepatitis B or influenza (see diagram). The goal of these microscopic manipulations is to develop a vaccine that will fool the immune system and make it swing into action. A smallpox preventive that expresses a herpes trait, for instance, will provoke the body into creating antibodies against herpes. The person is then protectively armed against an actual attack of the disease.

When tested in rabbits, the genetically engineered formulas proved to be able deceivers, eliciting large quantities of antibodies to hepatitis B, herpes simplex or flu. More impressive still was a study performed by a team at the National Institute of Allergy and Infectious Diseases (NIAID) showing that chimpanzees immunized with the genetically engineered hepatitis vaccine remained healthy when exposed to the disease. Paoletti got similar results when he exposed immunized mice to herpes virus, which can be fatal to rodents. Says he: "Even with ten to 20 times the lethal dose of herpes simplex, we have 100% survival."

The advantages of this piggyback approach to creating vaccines are enormous. First, there is no risk of actually getting herpes, hepatitis B or influenza from the injection, since the viruses themselves are not present in the formula. Second, the smallpox vaccine, however it is altered, is cheap, easy to use and does not require refrigeration--all tremendous advantages in Third World countries, where infectious diseases are rampant. "It would cost about 300 a shot, and only one shot would be required," says Molecular Virologist Geoffrey Smith of the NIAID team. By contrast, an injection of a hepatitis-B vaccine currently costs $100, and two or three doses are necessary.

Perhaps the greatest advantage of the new method is the possibility of creating a single vaccine that would be effective against a dozen or more different diseases. The cowpox virus is so large, says Paoletti, that "there is enough room to insert twelve to 15 different foreign genes. We could perhaps develop a polyvaccine that would render a person immune to herpes, hepatitis, malaria and other diseases, all in one shot."

But Paoletti believes that it will be at least three years before the vaccines can be tested on humans and several more before they can be marketed. In addition, he notes, there is no evidence that the herpes vaccine will help the 20 million Americans who already have the disease. "I think there is no question that this is a potential method of prophylaxis, but we cannot yet speak to the question of cure."

Other scientists have much graver doubts about the health department's work. "While this represents an elegant piece of genetic engineering, I have some reservations about the safety of using vaccinia," warns Virologist Edwin D. Kilbourrie, of Mount Sinai Hospital in New York City. "The risks are remote and rare," says Pediatric Immunologist Vincent Fulginiti of the University of Arizona, but he agrees with Kilbourne. The danger: vaccinia can be transferred by contact from the site of inoculation to the eye, other parts of the body and even to other people, sometimes causing infection. In individuals whose immune systems are damaged--burn victims, leukemia or AIDS patients--this could be lethal.

Paoletti admits that his newly engineered vaccines may not be for everyone, but believes that with a little restructuring they could be improved. "We may be able to delete genes that are responsible for the undesirable side effects of vaccinia," he says. In short, the techniques of genetic alchemy that made the vaccines possible could ultimately be used to make them safer.

In another feat of genetic engineering announced last week, researchers isolated the bacterial gene for a poison believed to cause toxic-shock syndrome. The disease made national headlines in 1980, when it caused the sudden death of 42 people, most of them menstruating women (cases in men are rare). Last year ten deaths were reported. In a paper published in Nature, three leading researchers concluded that the disease is produced by a toxin made by the common bacterium Staphylococcus aureus. Only about one in 1,000 adults is susceptible to the toxin, according to the authors. By isolating and then replicating the gene for the toxin, scientists will be able to make large quantities of the poison, which can then be used to develop a simple blood test to detect susceptibility. According to Microbiologist Richard Novick, director of the Public Health Research Institute of New York City, the screening technique could be ready for study within six months.

Those found to be vulnerable would be warned of the early signs of the disease-sudden high fever, dizziness and vomiting or diarrhea. Women might be advised not to use tampons, which have been associated with the bacterial growth that leads to toxic shock.

--By Claudia Wallis This file is automatically generated by a robot program, so viewer discretion is required.