A better way to make flu vaccine.

Health and medicine explained.
Feb. 7 2006 1:57 PM

Forget the Chicken and the Egg

A better way to make flu vaccine.

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Vaccinating chickens

Editor's note: This piece used phrases that appeared in a Nov. 5, 2005, article by Kitta MacPherson in the Star-Ledger of Newark, N.J., without citing or acknowledging that article. Slate apologizes to Ms. MacPherson.

To protect the world against bird flu, we need a vaccine for both birds and people that can be made quickly and that immunizes against several different strains of the virus. The current antiquated process for making flu vaccines succeeds on neither front. A new method described in the British journal Lancet this week, however, could. Its preliminary success suggests that vaccine makers should switch over as quickly as possible to modern techniques using reverse genetics.

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The new vaccine, the second of its kind to be reported this year, takes a benign human cold virus (adenovirus) and genetically alters it to resemble the dreaded H5N1 bird flu; the results produced in mice 100 percent immunity to several strains of flu. In light of this strong immune response, the adenovirus vaccine is likely to prove useful in humans. It could cut down the lead time for vaccine manufacture significantly and cover a larger number of virus subtypes. President Bush's $7.1 billion plan for preparing for a flu pandemic included $2.7 billion for flu-vaccine research; $3.8 billion of the total was approved by Congress for 2006. This week, the president asked for another $500 million for research for 2007. Some of the money should help us transition to the adenovirus vaccine, or another one like it. But far more government involvement is needed to ensure that the transition is quick and effective.

After clueless unprepared hospitals, vaccine production is the weakest link in the world's flu-preparation chain. Genetic recombinant and cell culture techniques like the ones that were used to make the adenovirus vaccine have been used routinely since the 1980s to make vaccines for other viruses, like chicken pox and hepatitis B. But the United States still produces all influenza vaccines, including potential bird-flu vaccines, using the creaky chicken-egg method created almost 50 years ago.

Why do we still rely on the chicken eggs? Vaccine manufacturers have been leery of making new flu vaccines since 1976, when fear of another pandemic like the 1918 Spanish flu led to the rushed production of an imperfect vaccine against a new swine flu. The vaccine manufacturers of the time (there were then 27) refused to make a vaccine for the swine flu until Congress assumed responsibility for all related liability. A political battle ensued. The drug companies won, and vaccine production began with the goal of inoculating more than 200 million Americans. But after 40 million got shots, several hundred cases of a life-threatening neurological paralysis (Guillain-Barré syndrome) occurred. Flu-vaccine production was hastily halted, and thereafter any rush to vaccinate has been labeled risky by the manufacturers. In December 2005, Congress gave companies liability protection for vaccines and drugs that target pandemic flu or bioterrorist attacks. Even so, drug companies, which have been criticized lately on issues of drug safety, are not eager to take on a potentially fallible vaccine that is not very profitable and will clearly be a public-relations nightmare if it fails.

But there are urgent public health reasons to overcome that reluctance. Here's how the state-of-the-art methods work: In reverse genetics, you don't need to work from the original strain of the virus. Instead, you approximate the virus but leave out its deadly properties. In the case of bird flu, for example, scientists can genetically engineer another virus to look like H5N1, by inserting strips of H5N1 genetic material. Averting a killer virus that can kill the cells in which it is growing saves time. Once the virus is engineered, scientists don't need to harvest millions of chicken egg embryos to grow it in. Instead they use mammal cells, which are easier to get.

In the "cell culture" step of the process, the cells are kept alive in big vats of nutrient solution while the newly made virus multiplies. As the cells reproduce, so does the virus. Eventually, the outer wall of the cell is removed, and the viruses are harvested, purified, and then neutralized. Once dead, they can safely be injected into subjects as a vaccine, which induces an animal or person to make the desired antibodies. With this method, the time from identification of a virus to the production of a batch of vaccines is just one month, compared to several months for the chicken-egg method.

Other new approaches are in varying stages of research. One vaccine that's still several years away from clinical trials targets the M2 protein of the influenza molecule. Since that molecule doesn't change, this kind of a vaccine might provide immunity to all flus (including bird flu) for a decade, rather than one flu for only a year. This huge improvement in flu vaccination would be a great return on investment.

And then there's the work of José Galarza. In a tiny lab perched above the Hudson River, Galarza has been experimenting with specks of genetic matter for nearly 10 years without big grants or federal funding. He works with microscopic blobs of genes (called viral-like particles) from which he fashions painless, oral vaccines. (Editor's Note: The following phrases from the three preceding sentences appeared in Kitta MacPherson's Nov. 5, 2005, article in the Star-Ledger: "In a lab perched above the Hudson River," "José Galarza has been experimenting with tiny specks of genetic matter for nearly 10 years," and "Galarza continues working with microscopic blobs of genes." Slate apologizes to Ms. MacPherson.) Galarza believes he can command his VLPs to knock out any kind of flu in lab animals—and potentially in humans—more quickly and safely than conventional vaccines. His work is in preliminary stages and difficult to evaluate against the current flu risk. But it is certainly worth our tax money to find out if he, and others like him, are right.

Currently, there are only three U.S. manufacturers making flu vaccine. We cannot depend on them alone to make the needed shift to the latest techniques. The solution is more government involvement. We should follow the example of the countries of Western Europe, whose governments take responsibility for the flu-vaccine process from beginning to end and assure the drug makers a certain return every year. Western Europe didn't suffer the yearly flu-vaccine shortage that the United States did in two out of the last three years. The new vaccine in the Lancet study is one of several that could soon add significantly to our arsenal against influenza. We have the technology. Now we need the political muscle to make sure it gets used.

Marc Siegel, M.D., is a professor of medicine and medical director of Doctor Radio at New York University’s Langone Medical Center.

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