How to make an avian-flu vaccine.

Answers to your questions about the news.
Aug. 10 2005 5:59 PM

How To Make an Avian-Flu Vaccine

First, make the virus bird-safe.

On Friday, a group of scientists announced that they had successfully tested a vaccine for avian influenza. Clinical trials aren't done yet, but the U.S. government has already announced that it's purchasing millions of doses of the experimental medication. How did the scientists come up with a vaccine?

By tweaking the recipe for ordinary flu shots. All influenza viruses share a common eight-gene structure and belong to one of three virus categories. Type A flu viruses, including avian flu, infect animals and occasionally humans. Type A viruses are further classified based on the type of hemagglutinin and neuraminidase surface proteins they contain. The avian-flu virus gets its name—A(H5N1)—from this combination of HA and NA proteins.

Scientists create most flu vaccines by isolating a virus from the cells it has attacked, cultivating it in a hen's egg, and then inactivating it with formaldehyde.The "dead" virus is then injected into a person in the hope that the subject's body will try to fight it off by creating antibodies. The presence of these antibodies helps the body prevent subsequent infections.

Creating the avian-flu vaccine, however, required an extra step. Because the virus kills birds, it won't grow in hen eggs in its normal state. Instead, scientists must reconstruct a bird-safe version of the virususing a technique called reverse genetics. (It's also sometimes called "targeted gene disruption.")

First, they extract the two genes responsible for encoding the virus's HA and NA proteins. They then extract one segment from the HA-producing gene—the segment of the gene that's harmful to birds—before inserting the two excised genes into DNA loops. These DNA loops are then combined with loops that contain six genes from another flu virus. (Many labs collect these six genes from a strain of influenza that first appeared in 1934 because it thrives in eggs.)

This new combination of eight genes is called a seed virus—essentially a new flu strain that will replicate easily in an egg. Once the seed virus is inserted into the egg, it attaches itself to a cell, hijacking the cell's resources and forcing it to make a new virus that contains the genetic material of the original virus.

When there's a sufficient amount of the seed virus, it gets injected into healthy volunteers as a vaccine. By monitoring their antibody response, experts determine the volume of vaccine that each flu shot should deliver. A normal flu shot is about 0.5 ml; so far, the avian flu vaccine requires a dose about 12 times that size.

Vaccines are never the final word on protecting people from the flu. Although avian influenza doesn't mutate as often as the common flu, it can still undergo something called antigenic shift. That happens when two different flu viruses exchange genetic material within a cell, resulting in a new combination of HA and NA proteins.

Explainer thanks Dr. William Schaffner of Vanderbilt University.

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