By David Shook Flu season is here, and, for the second straight year, supplies of the vaccine to guard against the virus are temporarily inadequate for the demand. Doctors are trying to target the initial shipments primarily at the elderly and those with pulmonary disorders or weakened immune systems. Not everyone will get the shot on time.
Last flu season, supplies were so tight that many people didn't get their shots until January. By then, the virus had begun circulating through many U.S. cities, infecting 10% to 20% of the population and leading to some 20,000 deaths, as it does nearly every year.
Vaccine makers, mindful of last year's problems, are shipping more doses than they did at the same time a year ago. Yet demand could be far greater than anticipated because of the recent bioterrorism attacks. Flu symptoms mirror the early signs of inhalation-anthrax infection. In fact, one of the Washington (D.C.)-area postal workers killed by inhalation anthrax was originally diagnosed as suffering from flu.
VIRAL DETECTIVES. New York Mayor Rudolph Giuliani has urged New Yorkers to be inoculated against the flu. His reasoning follows the advice of many infectious-disease experts. "Our concern is that emergency rooms are going to be overwhelmed once people start getting flu-like symptoms," says Dr. Robert Hudson, vice-president and medical director for ZymeTx (ZMTX), an Oklahoma City company that tracks the annual flu epidemic and has developed a testing device for the disease.
When it comes to the anthrax scare, influenza-detection products may be more pertinent than vaccines. These devices can let doctors know right away whether a person has the common flu virus. "If we have a sudden high number of people coming into emergency rooms with flu-like symptoms, but we test for the flu and find that these people don't have it, then we know something else is going on," explains Hudson. His company is one of several that make such devices, which some hospitals are already using. If vaccinations help more people to ward off the virus, fewer people run the risk of being misdiagnosed.
So why not have the 80 million doses of vaccine that are needed each year ready by, say, Oct. 1? Despite having been used for decades, the vaccine isn't getting any easier to produce. Each year, the development process faces a number of obstacles, not the least of which is that the vaccine must be reformulated as the virus itself changes.
There is some good news: Working on the flu shot might give vaccine makers some clues that will help them meet the challenges posed in the new age of bioterrorism.
EDUCATED GUESS. The flu vaccine is composed of parts of several different strains of the disease -- a combination of the bugs that were prevalent the prior year and the newer strains floating around the Southern hemisphere from April to September. "Summertime in the U.S. is winter flu season in the Southern hemisphere," says Dr. Richard Duma, director of infectious diseases for Halifax Medical Center in Daytona Beach, Fla. "Up here, in the fall we usually wind up getting many of the strains circulating down there during our summer months."
Different types of influenza A and B are collected by the Centers for Disease Control & Prevention, and then a single vaccine is formulated for the next flu season. The formulation is an educated guess, however. There's no sure way of predicting the specific genetic makeup of the next strain of influenza. Admits Hudson: "Basically, we're trying to guess the composition of a mutating virus as we're producing the vaccine."
They must be doing a good job of guessing: The vaccine is effective at least 70% of the time. Fortunately, the virus hasn't gone through a drastic shift in genetic makeup in decades. Minor shifts are common, but the last deviation occurred in 1918, when 20 million people died worldwide from a virulent form of influenza.
GOOD EGGS. As hard as it is to formulate the vaccine, making it is even trickier. The virus strains chosen for the vaccine are grown inside chicken eggs, the ideal environment for quick replication. At manufacturing sites in the U.S. and Britain, three companies make the vaccine using millions of chicken eggs -- each injected with the CDC's viral recipe. "Imagine a rack of eggs on a conveyer belt with a bank of syringes puncturing each egg and injecting it with live virus," says Len Levander, spokesman for Aventis-Pasteur (AVE), one of the flu-vaccine producers.
Sometimes the incubation process can take longer than expected, which was the case last year with the more virulent influenza A strain, according to Curtis Allen, spokesman for the CDC in Atlanta. Adds Aventis' Levander: "You're talking about Mother Nature. There's a limit to how much technology can help us."
This year, only American Home Products (AHP) experienced problems with the influenza A strain. As a result, AHP will ship slightly less vaccine than it did in 2000 -- and much of its 24 million doses will arrive several weeks late. "We're dealing with a living organism, and it's difficult to predict how it will behave in a test tube," says Doug Petkus, spokesman for Wyeth-Ayerst, the AHP division producing the vaccine.
SCANT FUNDING. Once grown inside the eggs, the flu batches are harvested and killed during a sterilization process. The sterilized virus is filtered from the egg fluid and concentrated to be turned into the vaccine. Lots are then shipped to the Food & Drug Administration for testing. If the process -- from CDC formulation through FDA review -- takes too long, come November not enough vaccine is available for everyone who wants a flu shot.
These obstacles hint at why so few companies are involved in vaccine development. Also, it's not a highly profitable business, so companies aren't willing to risk entering the field. Very little government funding goes into vaccine research compared with research for AIDS or cancer drugs.
Just four companies were making flu vaccine -- then Parkdale, a division of General Injectable Vaccines, dropped out of the business in 2000. This points out how low a priority vaccine development has become in the U.S. Along with Aventis-Pasteur and AHP, British biotech concern PowderJect is the only other company now making flu vaccine.
TOUGH PROMISES. Clearly, many factors could combine to make it difficult to get the anthrax and smallpox vaccines into wide-scale production, as the government has pledged to do in the wake of the bioterrorism attacks. While Washington has promised to have enough smallpox vaccine for the entire U.S. population by next year, it hasn't yet done so for anthrax because of safety issues surrounding that vaccine. And the smallpox pledge hasn't included any details about how 250 million doses will be proven safe and effective by the FDA before the end of next year.
Doctors say science may eventually overcome the inefficiencies associated with the flu vaccine, perhaps rendering the current system obsolete. Already, antiviral flu remedies can be taken at the onset of symptoms, improving the chances the infection won't keep people in bed for more than several days or lead to pneumonia.
What's more, flu vaccines that don't require shots are being tested. One is a nasal vaccine that uses a live virus rather than a dead one. Live viruses generally create a stronger immune response.
The flu may seem like a minor concern when a nervous nation is keeping watch for anthrax. But in many ways, the prevention and detection of the common flu virus illustrates the challenges confronting vaccine researchers. While flu prevention is far from perfect, it has at least made enough progress to provide some ideas about the best ways to prepare for other scourges -- be they the work of man or old-fashioned acts of nature. Shook covers biotechnology issues for BusinessWeek Online. Follow The Biotech Beat every week, only on BW Online