Bird Flu Alarm

2006-04-01-Bird-flu vaccine is no cure-all

Understanding Avian Influenza

2006-04-01-Bird-flu vaccine is no cure-all

The federal government has developed a human vaccine against the H5N1 bird flu, but it is only moderately effective, hard to make, and probably would not protect against emerging strains of the fearsome virus.

The new vaccine, produced by Sanofi Pasteur in Swiftwater, Pa., under a $150 million federal contract, is "a small step" toward being prepared for a possible global flu epidemic, said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which funded the vaccine research.

A study of the vaccine published in today's New England Journal of Medicine found that it stimulated a meaningful immune response only about half the time - and only in healthy adults given two high doses over 28 days. In contrast, a single low-dose seasonal flu shot is 75 percent to 90 percent effective.

This low potency, coupled with the fact that the vaccine is grown in chicken eggs - the same problematic technology used to make seasonal flu vaccine - means that barely 1 percent of the world's population could be immunized even if worldwide production were ramped up.

"This isn't going to be the vaccine that's going to protect us," said Gregory A. Poland, an infectious-disease and vaccine researcher at the Mayo Clinic who wrote an editorial that accompanies the study.

Despite the vaccine's limitations, U.S. health officials are going ahead with plans to stockpile enough to immunize about four million people, Fauci said at a news conference this week.

That would cover high-priority groups - notably health-care providers and vaccine-plant workers - and provide "a very tenuous stopgap" if a pandemic hit soon, Fauci said.

The H5N1 virus has decimated bird flocks in Central Asia, Eastern Europe and Africa over the last year. So far, it has not mutated into a flu that can spread easily from person to person, even though almost a decade has passed since it first jumped from chickens and killed seven people in Hong Kong.

If the virus becomes contagious among people, experts say, the impact would be calamitous. Humans have no natural immunity against H5N1 - of the 176 confirmed human cases in seven countries, 97 have died - and the ever-changing virus has resisted antiviral drugs.

Scientists are racing to create vaccines, and at least 30 promising drugs are in the pipeline, including some that would make cumbersome egg-based production obsolete.

But the race involves many obstacles and controversies, as the new vaccine shows.

Studies suggest the H5N1 strain - named for the particular combination of enzymes that enables it to break in and out of cells - does not activate the immune system as much as other flu strains. That is one reason the new vaccine requires 12 times the dose used in seasonal flu vaccines to be effective.

To try to increase vaccine potency, researchers have been adding an adjuvant - a substance that helps the immune system recognize invaders.

Sanofi Pasteur is now trying the new U.S. vaccine with an adjuvant - a test that Poland and other experts advocated in the first place. Sanofi's French division is also testing an H5N1 vaccine, with and without an adjuvant, under a contract with the European Union.

Chiron, a California-based vaccine-maker, has said an adjuvant is a key ingredient in the vaccine that it is developing for the U.S. government. About 10,000 doses are expected to be delivered within a few months, according to the National Institute of Allergy and Infectious Diseases.

Even as stockpiles are being built, officials worry the drugs will be outmoded if the virus undergoes significant changes. Federal researchers have reported that a human infection in Indonesia last year was caused by a genetically distinct strain of H5N1.

Probably, Poland says, an effective pandemic vaccine would need to ward off several threats, as does the seasonal flu vaccine.

Health officials are considering adding an H5N1 vaccine to the seasonal version, in hope of "pre-priming" a human immune response, Fauci said. But not only would that deplete the scarce new vaccine; it also could expose people to a drug they might never need.

While the new vaccine seemed safe in tests, officials recall the "swine flu" debacle of 1976. The government had to halt a vaccination program that led to 25 deaths - for a pandemic that never came.

"The good news is that we have a vaccine that can induce an immune response," Fauci said. "But the sobering news is... we have a long way to go."

Understanding Avian Influenza