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Researchers Seek a New Method for Making Flu Vaccine

When it comes to making influenza vaccine, there seems to be a crack in the system. Although dependable since the 1970s, the current practice of injecting flu virus into fertilized hens’ eggs requires at least six months—and hundreds of millions of eggs—to produce a sufficient supply of vaccine for the U.S. population. If an emergency should arise—such as this year’s flu vaccine shortage or the appearance of a deadly form of bird flu—there is currently no way to boost the vaccine supply quickly.

Photo of animal cells growing in a bioreactor
Animal cells growing in a bioreactor
Credit: ID Biomedical

“The egg method isn’t very flexible if you need to rapidly ramp up vaccine supply,” says Jonathan Seals, Ph.D., director of Process Development at ID Biomedical Corporation of Northborough, MA. “Vaccine manufacturers need to arrange for egg supplies months in advance—and you can’t tell a chicken to lay more eggs.” ID Biomedical was recently awarded a $9.5 million contract from NIAID to study an alternative method, called cell culture, for rapidly producing large quantities of flu vaccine.

With the egg method, each of the three targeted flu strains for a given year is injected into separate fertilized eggs, where the viruses multiply. The three viruses are later harvested from the eggs, purified, and killed. Using a detergent, manufacturers “split” the viruses, releasing the surface antigens HA and NA to increase accessibility to the immune cells of the body. Finally, the three split viruses are combined to make one dose of flu vaccine.

According to Dr. Seals, the cell culture technique is a very interesting alternative as it is an efficient and flexible strategy for manufacturing influenza vaccines. Instead of injecting flu virus into eggs, they overlay the virus onto special dog kidney cells, which, unlike eggs, grow and multiply rapidly in the lab. The inoculated cells are then incubated inside a growth chamber called a bioreactor, adhering to small, round beads called microcarriers. (The cells must adhere to a surface in order to grow, and the round microcarriers provide a large amount of surface area for them to do so.) As with the egg method, once the virus-containing fluid is removed from the bioreactor, the virus is purified, killed, split, and then blended with the two other viruses to make doses of flu vaccine.

The advantages of the cell culture technique are that if the need should arise for increased amounts of vaccine, a manufacturer could simply thaw out more cells and perhaps add more bioreactors. In addition, unlike eggs, the cells are naturally sterile, which helps to control product quality. Finally, the nutrients in which the cells grow contain no animal serum, which reduces the risk of microbial contamination.

Dr. Seals says that even in a best-case scenario, however, we shouldn’t expect a cell culture vaccine for the U.S. population anytime soon. Currently, the research team is conducting studies to determine the optimal conditions under which the cell culture vaccine can be produced—studies that are tedious and that require the experimental variation of many factors. Keeping that in mind, says Dr. Seals, clinical trials of the vaccine are expected to begin in approximately 2 years.

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Last Updated February 27, 2007