How to Make a Better Vaccine

By Alice Park

More than half of the $7.1 billion that President Bush wants to spend preparing for a flu pandemic is dedicated to finding better ways to make antiviral drugs and vaccines, an investment that scientists say is long overdue. Flu vaccines were being grown in chicken eggs more than 50 years ago, and that's how they're still made today. It's a painfully slow procedure that takes about nine months, with much of that time devoted to the hit-or-miss process of incubating viruses in the chicken eggs.

One way to speed things up is to toss out the eggs and grow the viruses in human cells. Any virus that can infect humans will, by definition, grow easily in human-cell cultures, so that step could cut the incubation time to three months. Chiron, one of the world's leading manufacturers of the egg-dependent flu vaccine, is testing its first cell-culture technique, which it plans to apply to seasonal and pandemic flu vaccines. The Department of Health and Human Services last spring awarded a $97 million contract to Sanofi-Aventis, a Paris-based drug company, to develop avian-flu vaccines using human cells. The company is preparing a 20,000-liter bioreactor tank in the U.S. to brew test cultures. Jaap Goudsmit, chief scientific officer for Netherlands-based Crucell, which supplies cell-culture technology to Sanofi-Aventis, expects to test the first cell-based avian-flu vaccine as early as next spring.

Growing large batches of live virus, however, is a tricky business, and some scientists are turning to genetic engineering to improve the output. Tweak some genes, and you can make a virus that grows more easily in cell cultures. Tweak others, and the virus becomes a better target for the body's immune system.

But all these methods are just stopgap solutions, since a full-fledged flu pandemic would kill millions of people before the vats made enough vaccine to meet demand. Ultimately, vaccine makers may need to go straight to the source: the flu virus' genetic code. By extracting snippets of viral RNA and transforming them into DNA strands, scientists can in theory create a template for antibodies that can ward off flu. Researchers at PowderMed in Oxford, England, have created a DNA cassette into which they can insert genes from whatever flu virus is going around and, they say, have a vaccine ready in less than three months.

This plug-and-play approach borrows from gene therapy, in which tiny pieces of DNA are delivered directly to circulating immune cells in the bloodstream. The DNA packets are painted onto tiny gold pellets (an ideal delivery medium) and shot into the body at supersonic speeds with the press of a button on a gene gun. "In the event of a pandemic, you don't need health-care workers to deliver this vaccine," says Clive Dix, PowderMed CEO. "You could train people in 10 minutes." Early safety studies showed promising results, and PowderMed hopes to continue testing its vaccine against avian- and seasonal-flu strains next year.

Although the current threat of avian flu may have passed before the next-generation vaccines make it to market, the work won't be wasted. The upgrade will make even the annual flu vaccines more effective and will prepare us better for when the next pandemic threat looms. CURRENT METHOD: EGG CULTURE Virus is purified and chemically killed to produce the vaccine Virus --> Virus is grown in fertilized chicken eggs --> Vaccine NEW METHOD: HUMAN-CELL CULTURE Virus is killed and processed to produce the vaccine Virus --> Cell --> Virus is grown in human-cell culture --> Vaccine GENETIC METHOD: DNA VACCINES Plasmid is manufactured, purified and painted onto gold particles Virus --> Viral RNA --> Microscopic gold particles --> Gene gun shoots particles into the skin