Medicine: Made-to-Order Vaccines

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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."

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