The Vaccine That Flu the Coop

Only half the vaccine doses expected for this flu season will be available to the public. Although efforts are afoot to make sure that the elderly and other people who most need the shot get it, the ultimate impact of the surprise shortfall will depend on how nasty this year's virus turns out to be.

This Christmas season, Santa Claus might be leaving some unwanted presents under the tree: aches and fevery chills. With the paucity of flu vaccines, even Santa--at least, that is, one jolly old elf in Colorado Springs--couldn't get a shot. Shortages have driven the federal government to ration, making shots available only to those whom the flu hits hardest: children, the elderly, pregnant women, and health care workers who could potentially spread the virus. Although Colorado-based Santa Nick Pallotto will lift thousands of children onto his knee this holiday season, a local hospital turned him away because he is only 62--3 years younger than the cutoff for the people most at risk.

The U.S. Food and Drug Administration (FDA) expected more than 100 million doses of influenza vaccine to be delivered this season--until Chiron Corp. announced that 9% of its product was contaminated by bacteria. After inspecting the manufacturing plant in England, FDA officials announced that Chiron couldn't guarantee the purity of the rest of the batch, and production was shut down. That left only 54 million doses from Aventis Pasteur Inc. and 1.1 million doses from MedImmune available for public use--enough for about a third of the people normally encouraged to get vaccinated.

Although the individuals at highest risk of getting sick don't always get inoculated, the shortfall has driven the public into a vaccine-seeking frenzy--with good reason. Older people are more likely than the young to suffer life-threatening complications after coming down with the flu, and vaccinations significantly reduce the chance of getting sick. A recent Dutch study of 26,000 seniors aged 65 and up found that people who get vaccinated yearly are up to one-third less likely to die than those who don't.

To help bulk up the reserves, the two remaining manufacturers that supply the United States have also gone back to their factories. Aventis is generating another 4 million doses, and MedImmune plans to churn out an additional 2.6 million doses, which should be available in early December. "It's normal for vaccine manufacturers to have excess bulk material"--leftover virus that can be made into extra doses, says virologist Kathy Coelingh of MedImmune.

Other vaccine manufacturers are also pitching in. In late October, Merck tripled its production of pneumococcal vaccine to 17 million doses. Pneumonia, which can ride on influenza's coattails, often kills older folks who come down with the flu. So preventing this disease might boost survival in those seniors who can't avoid flu this season.

Although Aventis and MedImmune can throw in a few more million doses, the extended nature of the production cycle makes it impossible for manufacturers to simply goose their output to make up for the shortfall. Flu vaccines are grown in eggs, and manufacturers need to order special, virus-free chickens to lay those eggs a year in advance. Nor can producers stockpile vaccines: Every year, the virus changes its coat, and the previous year's vaccine loses its effectiveness. And with so few manufacturers on the job, contamination problems--which are always a risk--can turn disastrous. Only a handful of pharmaceutical companies produce influenza prophylactics because drugs that cure diseases make a lot more money than preventive vaccines do. And only a small number of consumers get their flu shots every year, says vaccinologist Samuel Katz of Duke University in Durham, North Carolina. "Vaccines are grossly undervalued," he adds.

Even if one manufacturer could cover another's shortfall, the pickup might not help those on the high-risk list because the three vaccines normally produced for the U.S. market aren't interchangeable. Each is licensed by FDA for use in the groups of people that the manufacturers have tested clinically. For example, Aventis's Fluzone has proven effective in people of all ages, but the nasal inhalant FluMist, made by MedImmune, has been tested only in healthy people between the ages of 5 and 49.

To save the Fluzone for the sick and elderly, the Centers for Disease Control and Prevention in Atlanta, Georgia, has recommended that FluMist go to healthy people, such as doctors and nurses. FluMist differs from the other vaccines because it contains live virus that has been hobbled so it can't make people sick. Because FluMist is live and because people spray it into their noses, the vaccine stimulates a broader immune response than the injected vaccines do. By the time people hit their 70s, however, their mucous membranes get a little dry--a situation that could prevent the live vaccine from doing its job. For now, MedImmune officials hope to license FluMist for use in people ages 50 to 64 and have just sent clinical trial data to FDA for consideration.

Some researchers think that the flu vaccine supply can be stretched by cutting the current dosage. In 2002, infectious-diseases researcher John Treanor of the University of Rochester in New York showed that half a dose of the type of virus recommended for the elderly stimulated an immune response to nearly the same degree as a full dose in young, healthy volunteers. If additional research supports this finding, perhaps vaccine doses could be tailored to the age and health of the individual. Other researchers are trying to determine whether less-than-full doses of flu vaccines would be effective if given in the skin rather than the muscle. A recent study showed that young people could mount a respectable immune response this way--although older people couldn't. Studies that show how protective the smaller shot is will not be completed in time to help this season, however.

Some vaccine developers hope to circumvent potential contamination. Vaccines produced in eggs have to be sterilized--the hens are hyperclean, but their eggs still carry bacteria--putting every year's supply at risk for spoilage. Growing virus in sterile cell cultures or generating a different type of vaccine in insect cells sidesteps bacteria entirely. Such methods could bulwark vaccines against catastrophic deficits: Cells for culturing viruses can be stored frozen and thawed when needed, no hens required.

So far this fall, few people have gotten sick, indicating a slow start to the flu season. "Things are quiet," says Katz, which could mean that the vaccine shortage might go untested by this year's virus. For many seniors, a mild flu season might be the best thing that Santa could leave under the tree.

Mary Beckman writes from southeast Idaho and barely has the sniffles so far.

Follow the flu season: http://www.cdc.gov/flu/weekly/fluactivity.htm

FDA's flu site: http://www.fda.gov/oc/opacom/hottopics/flu.html

Healthy People 2010: http://www.healthypeople.gov/