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Flu Busters

With nasal spray and gene guns, the chase is on to prevent the next pandemic.

By Wendy Orent // Fall 2005
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Nobody knows exactly how avian flu—the H5N1 strain that has killed millions of poultry and a handful of people—might evolve to spread widely among humans. But Daniel Perez, a flu expert at the University of Maryland, believes, like many others in the field, that a reassortment between a human virus and H5N1 would likely result in a pandemic. The best preventive tactic would be to vaccinate Asian poultry farmers against circulating human flu strains, preferably with live attenuated viruses like those in FluMist, a nasal spray. (If the farmers don’t get the regular human flu, reassortment can’t happen.) But use of the weakened virus would have to be monitored carefully, developed countries would need to underwrite the cost, and the vaccine is currently licensed for use only by people between five and 49 years of age who are not immunocompromised.

What’s more, the virus could theoretically evolve into a human disease without reassortment: If it were to begin passing directly from person to person, the virus might become a more effective human disease as it cycled, even without exchanging genes with an existing human flu virus. So stopping any threat of an H5N1 pandemic would require a vaccine that provided immunity against H5N1 itself.

Flu researchers at St. Jude Children’s Research Hospital in Memphis have taken the first step, genetically engineering a viral strain that, unlike wild-type H5N1, doesn’t kill the fertilized chicken eggs used to grow flu vaccines. In recent clinical trials, the vaccine has been shown to produce a strong immune response in human volunteers, indicating that it should protect against pandemic H5N1 flu—or at least the strains circulating now. The U.S. Department of Health and Human Services plans to build a stockpile of H5N1 vaccine.

Others favor more radical approaches, such as the “gene gun” developed by Stephen Albert Johnston of Arizona State University. This helium-powered device uses antigen-laced gold bullets just a micron in diameter that can be sprayed directly into the skin, where the antigens are taken up by dendritic cells, which play an important role in immunity. The gene bits on the bullets may allow long-term protection from any number of flu strains, so long as the sequences for the antigens of whatever strains are circulating are included. But this approach too needs much testing.

The cautious U.S. Food and Drug Administration favors the tried-and-true egg-based technology used since the 1930s to make flu vaccines. But DNA-based vaccines ultimately may prove stronger, quicker to produce and much more flexible, able to provide lasting immunity to any current or future flu strain.

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Avian influenza has sparked near panic over an imminent pandemic. But some biologists argue that the dread is overdone.

A Turn for the Worse

Here’s how the flu virus evolves to thwart natural resistance.

Avian Flu, One Year Later

After the panic, the author of our article on avian flu discusses developments in the story.

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