The threat of H1N1 swine flu appears to be abating, but the virus could come roaring back later in the year, and experts are now debating whether to produce a pandemic influenza vaccine. One key problem is that almost all of the world’s flu vaccine is produced using chicken eggs, and production capacity is severely limited. Many manufacturers are working on alternatives to the antiquated technology for vaccine production, but those will play a small role at best should the world be struck by a flu pandemic this year, World Health Organization vaccine expert Marie-Paule Kieny said at a news conference today. They could make a difference down the road, however.
Almost all seasonal flu vaccine is made using a clunky, 50-year-old process, in which companies adapt the virus to multiply in hens’ eggs, grow the virus, then break the eggs open and purify the key antigens needed to make vaccine, the hemagglutinin and neuraminidase molecules that stick out from the virus’s surface. In all, the process takes more than 5 months. This is also how the vast majority of a pandemic vaccine would be made.
Most vaccine companies are working on similar vaccines that are grown in mammalian cells rather than eggs. This has several advantages: Manufacturers are less dependent on the supply of chicken eggs—which is difficult to increase quickly and can become vulnerable during bird flu outbreaks—and it could shave 10 weeks off of the 22 weeks now needed to make a vaccine using eggs. It would also yield a vaccine that's safe for people with egg allergies.
But although more practical and cleaner, cell-based vaccines don't promise a major boost in production capacity. Moreover, success with the technique has been slow to come, despite more than $1.5 billion in U.S. Department of Health and Human Services contracts to several companies to fund clinical trials of cell-based vaccines and scale up manufacturing. Novartis is the only company that has begun building a cell-based vaccine plant in the United States, (in North Carolina), with the help of a $487 million HHS contract awarded in January. It should be operational by 2012. No cell-based vaccines have yet been licensed in the United States, in part because getting regulatory approval is complicated.
In Europe, at least three companies have licensed a cell-based vaccine, but none has actually started producing it so far. Solvay built a plant in a small town outside of Amsterdam several years ago, but technical problems have delayed the start of production. “In terms of quantity, globally, [cell-based vaccines] will represent only a small amount of the total,” Kieney said today.
Some alternatives could be faster to scale up. Furthest along is Protein Sciences Corp. of Meriden, Connecticut, which makes a flu vaccine by infecting caterpillar cells with a baculovirus carrying the gene for hemagluttinin. The company has completed late-stage clinical trials for its seasonal flu vaccine and expects to receive U.S. Food and Drug Administration approval this year; it plans to be making a swine flu vaccine in 5 weeks at its pilot production plant, says CEO Daniel Adams. This vaccine could potentially be produced in the world's many facilities for making pharmaceutical proteins, which could allow the production of enough vaccine for between 3 billion and 6 billion people in 3 months, says David Fedson, a retired drug company executive living in France.
Other recombinant vaccines that could truly lead to an explosion in production capacity are further off. VaxInnate, a company in Cranbury, New Jersey, is developing a flu vaccine made in E. coli, which requires far less volume for manufacturing than animal cells. It links a portion of the hemagluttinin protein to a bacterium's flagellin protein to boost the response from immune cells. CEO Alan Shaw says the company could make enough doses for the state of New Jersey in a reactor the size of the gas tank on a backyard barbecue.
"It's a much simpler production system," says influenza vaccine expert John Treanor of the University of Rochester in New York state. Treanor notes, however, that first this novel approach to stimulating immunity will require extensive clinical trials to establish that it's safe and works.