If you want to make an omelet, you have to break some eggs. And if you want to supply the U.S. with flu vaccine, you have to break about 100 million.
That may change someday, as leading vaccine manufacturers explore the possibility of trading their chicken eggs for stainless-steel culture vats and growing their flu virus in cell lines derived from humans, monkeys or dogs. The technology could allow companies to produce their vaccines in a more timely and less laborious manner and to respond more quickly in an emergency.
Today's flu vaccines are prepared in fertilized chicken eggs, a method developed more than 50 years ago. The eggshell is cracked, and the influenza virus is injected into the fluid surrounding the embryo. The egg is resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine. Even with robotic assistance, "working with eggs is tedious," says Samuel L. Katz of the Duke University School of Medicine, a member of the vaccine advisory committee for the U.S. Food and Drug Administration. "Opening a culture flask is a heck of a lot simpler."
Better yet, using cells could shave weeks off the production process, notes Dinko Valerio, president and CEO of Crucell, a Dutch biotechnology company developing one of the human cell lines. Now when a new strain of flu is discovered, researchers often need to tinker with the virus to get it to reproduce in chicken eggs. Makers using cultured cells could save time by skipping that step, perhaps even starting directly from the circulating virus isolated from humans. As an added bonus, the virus harvested from cells rather than eggs might even look more like the virus encountered by humans, making it better fodder for a vaccine, adds Michel DeWilde, executive vice president of R&D at Aventis, the world's largest producer of flu vaccines and a partner with Crucell in developing flu shots made from human cells.
Whether vaccines churned out by barrels of cells will be any better than those produced in eggs "remains to be seen," says the FDA's Roland A. Levandowski. And for a person getting jabbed in the arm during a regular flu season, observes Richard Webby, a virologist at St. Jude Children's Research Hospital in Memphis, Tenn., "it's not going to matter where the vaccine came from."
Where the cell-based vaccine will become invaluable, Webby states, is in the case of a global pandemic. Should a new strain of flu crop up outside the normal season--one that is different enough from previous strains that people will have no immunity--cell-based systems will allow health officials to respond more rapidly. "Cell cultures are a lot easier to scale up faster," he explains. Technicians would simply remove cells from a freezer and grow them in large volumes--something that is not possible with chicken eggs. Although flocks of chickens kept in clean environments are available almost year-round, companies generally place their egg orders six months before they start vaccine production. And preventing a pandemic could require 10 times as much vaccine as a normal flu season. "If halfway into manufacturing, you need a billion more eggs, you're not going to get them," remarks Wayne Morges, a vice president at Baxter in Deerfield, Ill.
Preparing vaccines in cell cultures is not new. Aventis, for example, currently produces polio vaccines in the same monkey kidney cells that Baxter is gearing up to use to produce flu injections. And Baxter used the monkey cell line to replenish the U.S. supply of smallpox vaccine. So converting to cell-based systems, Katz says, would be "moving flu vaccine production into the 20th century at the beginning of the 21st."
Why has it has taken manufacturers so long to come around to considering cell-based systems? Perhaps because current egg-based systems work so well, Webby surmises. Up-front costs for preparing production plants to function with cells rather than eggs might also be an impediment.