Vaccines Stage A Comeback

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One of the inventors of the gene gun thinks that shooting viral DNA could someday replace traditional vaccines. Dr. Stephen Johnston, director of the Center for Biomedical Inventions at the University of Texas Southwestern Medical Center in Dallas, is using medicine's newfound skill at sequencing genomes to figure out precisely what genes express, or turn on, when a bug first enters a host's cells. Using microarrays, also known as "DNA chips," Johnston is working to identify those genes, then snip them from a pathogen's genome and use them, or the proteins they make, as vaccines to trigger an immune response.

A similar strategy could lead to vaccines against malaria and TB. But while conquering such hitherto vaccine-resistant diseases would be dramatic, it would be positively revolutionary to extend vaccines to illnesses that have seemed beyond their reach. One such candidate is heart disease--which may involve the immune system in ways nobody ever imagined just a few years ago. The buildup of fatty cholesterol deposits on artery walls may begin, it turns out, with an inflammation perhaps caused by bacteria. This immune response alters the arteries in ways that make them prone to cholesterol damage. A vaccine that could prevent the initial infection or tamp down the inflammatory response might, doctors believe, prevent the chain of events that leads to heart attacks from getting started in the first place.

Cancer would seem to be the last disease you could prevent or treat with a vaccine. After all, infection plays no role in cancer, except in a few rare types of malignancy. And a cancer cell, unlike an invading pathogen, isn't wholly foreign to the body. Nevertheless, researchers are learning that the immune system can even be trained to go after tumors. CanVaxin, for example, a vaccine for the deadly skin cancer melanoma, is made from cancer-cell lines taken from three different patients; among them, they express more than 20 disabled tumor antigens that the immune system can learn to recognize.

"What we've been able to show," says Dr. Guy Gammon, vice president of clinical development for CancerVax, the biotech company that makes the vaccine, "is that not only do a majority of patients make an immune response, but that those making a strong response survive longer."

Indeed, in early clinical trials on people whose tumors had been surgically removed, those receiving the vaccine lived on average twice as long as controls. To make the vaccine even more potent, company scientists are testing a version of CanVaxin enhanced with cytokines to help boost the response of patients with immune systems damaged by chemotherapy. In Canada a vaccine called Melacine, made by Corixa, is also fighting melanoma, shrinking tumors as effectively as chemotherapy but with fewer side effects. It is currently in trials in the U.S.