China Enters Bird Flu Vaccine Race

'Whole-Virus' Approach Spares Hard-To-Get Ingredients

(WebMD)  Chinese researchers report that a new bird flu vaccine shows promise in early human tests.

Like the previously announced Glaxo and Sanofi bird flu vaccines, the Chinese H5N1 bird flu vaccine is given with an immune-boosting substance called an adjuvant.

Jiangtao Lin, M.D., of Beijing's Chinese-Japanese Friendship Hospital, and colleagues tested various doses of the vaccine in 120 adult volunteers aged 18-60. They found that it worked best when given in two 10-microgram doses four weeks apart.

That's better than the Sanofi vaccine, which needs two 30-microgram doses. But it's not as low an effective dose as that reported for the Glaxo vaccine, which needs two 3.8-microgram doses.

Why is a low dose important? In an editorial accompanying the Lin report, British infectious disease specialist Iain Stephenson, MRCP, notes that if there's a bird-flu pandemic, the world will need hundreds of millions of doses — fast. This means scientists will be trying to make as much of the vaccine's main ingredient — the vaccine antigen — as quickly as possible. The lower the dose, the more doses you get. That's why researchers striving for a bird flu vaccine are looking for "dose-sparing" techniques.

Based on the seasonal flu vaccine, Stephenson estimates, current manufacturing processes could produce about 900 million 15-microgram doses of bird flu vaccine in six months. At two doses a person, this means 450 million people could be vaccinated within six months of a pandemic. A person would be protected only after the second dose, given one month after the first.

The Chinese vaccine, made by Sinovac Biotech Co. Ltd. in Beijing, uses a different approach than other experimental bird flu vaccines. Instead of using just the H5 protein — in what's known as the "split virion" approach — the Sinovac vaccine uses a whole killed virus. The vaccine virus is genetically engineered to lack the virulence gene that makes it lethal to the hen's eggs in which it is grown.

The Glaxo vaccine seems to offer more doses for less antigen: 3.8 micrograms versus 10 micrograms per dose. However, the Glaxo vaccine uses the split-virion approach. Lin and colleagues note that making a flu vaccine this way wastes 20 percent to 30 percent of the vaccine antigen.

On the other hand, whole-virus vaccines tend to cause more side effects than split-virion vaccines. In their clinical trial, Lin and colleagues did not see any troubling side effects. But they have not yet tested the vaccine in children, who tend to have more side effects with whole-virus vaccines.

Stephenson notes that the world's current flu vaccine manufacturing process is geared to make split-virion vaccines. A change to whole-virus vaccines would mean lots of new equipment and new regulatory hurdles.

Of course, nobody has yet proved that any bird flu vaccine will protect a person against the disease. The ultimate test will come only if the bird flu virus learns to spread among humans.

Lin and colleagues report their findings in the Sept. 7 online issue of The Lancet.


SOURCES: Lin, J. The Lancet, Sept. 7, 2006; early online edition. Stephenson, I. The Lancet, Sept. 7, 2006; early online edition.