President Bush speaks at the National Institutes of Health

A major part of President Bush's new plan to fight pandemic influenza is devoted to speeding development of modern technology to produce flu vaccines. He calls for the U.S. government to invest more than one-third of his $7 billion spending request on such novel processes, particularly one that makes flu vaccines more quickly by using the cells of mammals instead of the older, slower method of using chicken eggs.

Fears of an impending global flu pandemic have prompted biotechnology companies to step up research into faster ways to manufacture vaccines. Now, the Bush administration is asking Congress to spend nearly $3 billion to push the effort.

A vaccine contains a disease microbe, called an antigen, inactivated or weakened so that it is not infectious when injected into a person. The immune system sees the antigen as an enemy invader and rallies its troops, the white blood cells, to neutralize and kill it. A vaccine is essentially a training program that teaches the immune system what to look for when the real disease enters the body.

U.S. Health and Human Services Secretary Michael Leavitt told a Senate committee that the purpose of President Bush's new vaccine research program is to identify a large variety of promising new technologies.

"We'll begin to invest in those technologies in the first round, then we'll go back and say, 'Which of them continue to show promise after our first investments?' and we'll begin to narrow our investments. We are programming to have multiple providers and to utilize the best technologies that come from a wide range of starts," he said.

The traditional method of making flu vaccines relies on fertilized chicken eggs, a technology little changed since the 18th century. In this method, the most common strains of the virus are injected into eggs 11 days after fertilization and accumulates in the fluid surrounding the embryo. Each strain is grown in separate eggs. The embryo becomes infected and the virus multiplies. After several days of incubation, machines open the eggs and harvest the virus, which is purified, chemically inactivated, and used to produce vaccine.

Since it takes one or two eggs to make a single vaccine dose, many millions of eggs are needed to make a vaccine for a large population.

Another drawback is that the entire process is slow, taking up to nine months. But the director of the U.S. National Vaccine Program Office, physician Bruce Gellin, told the Senate panel that it is inexpensive and reliable.

"The concept here is that we have a tried and true methodology to make vaccines in that we know at the end of the line, it is the component of the vaccine that stimulates an immune response," said Dr. Gellin.

Dr. Gellin adds that the drive to develop a speedier replacement for egg-based flu vaccines is focusing on substituting the cells of mammals for the eggs.

"The conversion to a cell-based system is essentially to do the same thing in a more modern way, using cells to grow virus. At the end of the line, you still have that same antigen," he explained.

With this method, the virus is injected into cells instead of eggs, preferably kidney cells from a mammal such as a monkey. The virus multiplies as it does in eggs. Machinery then removes the cells' outer walls and, as in the egg process, purifies and chemically inactivates the virus before it is put into a vaccine.

A flu shot

The U.S. government says this method is better than using eggs because manufacturers can freeze cells in advance and then thaw and grow them in large volumes in the event of a pandemic. This allows more vaccine than by the egg-based procedure. There is no wait for egg fertilization and no delivery time from farm to factory. A consultant to the U.S. health industry, David Webster, says these advantages shorten production time to five or six months.

"The cell based technology is much faster. When it comes to pandemic flu, speed matters. Delays can result in a great number of deaths," he said.

This process is used for polio and rabies vaccines, but is still in the experimental stages for flu vaccine. Why?

"The reason it hasn't been used in the United States is that it is a more expensive manufacturing technology," added Mr. Webster.  "The low cost technology has been instrumental in increasing immunization rates."

The Bush proposal seeks to end the dominance of egg-based flu vaccines, but the alternative will take time because of the need to perfect the process, test it in people, and expand manufacturing capability.