OPTIONS VI: Tests of Flu Vaccine Too Variable for Reliability

TORONTO, June 18 -- The tests used to evaluate influenza vaccines are so unreliable they can vary up to 700-fold from one lab to another, a British researcher said here.

Because experts fear the world may need a vaccine against a new flu pandemic at a few months' notice, such unreliability can't be tolerated, said John Wood, Ph.D., of the United Kingdom's National Institute for Biological Standards and Control.

The issue is "brought to a head when there are global influenza vaccine trials taking place," Dr. Wood said at the Options for Control of Influenza meeting.

"If you want to compare a clinical trial in Canada with one in Europe," he said, "where do you start?"

There are two main tests used to evaluate the effectiveness of flu vaccines, Dr. Wood said -- hemagglutinin inhibition and antibody neutralization. But both tests are surprisingly variable.

Form lab to lab, he said, the results of the hemagglutinin test vary between six- and 128-fold "and the neutralization test was even worse - a 91- to 720-fold variation between labs."

To try to remedy the situation, he and colleagues -- working with the World Health Organization - are planning an international study to create a reference standard.

Part of the problem, he said, is that "there are so many variables - interactions with antibodies, with the virus, with red blood cells." Even using different sources of red blood cells - as many labs do - can cause variation, he said.

Dr. Wood and colleagues have collected four liters of serum from human volunteers exposed to various experimental H5N1 vaccines, all of whom had high antibody responses.

The serum will be freeze-dried and distributed to labs around the world for testing as a reference standard, probably starting this fall, he said. "It's a small study with a panel of test sera to see how well this standard performs in making the results more reproducible," he said.

Health authorities currently avoid the issue, he said, by having many labs test a given seasonal vaccine and then deciding how effective it will be by consensus.

Now, though, the issue is more highly charged, as many authorities fear that a pandemic influenza strain is overdue. The highly pathogenic H5N1 avian flu strain - already seen in many parts of the world - is viewed as a possible pandemic candidate and much research has been done on finding vaccines against it.

But studying those vaccines - using the standard techniques - has been difficult, agreed Keiji Fukuda, M.D., of the World Health Organization's influenza program.

He said standardizing the development of vaccines would be a mistake, but "there's the whole issue of how do you know whether one vaccine is comparable to another."

Dr. Wood had raised the issue during a wide-ranging plenary session addressing international pandemic preparedness, in which other speakers warned that:

• Africa is woefully unprepared for a flu pandemic, especially if it arises from the current H5N1 avian flu strain that has been seen in nine African nations.
• Wrangling over intellectual property could harm the global effort to create effective pandemic vaccines.

"Influenza has never been a priority for Africa," said Stella Chungong, M.D., of the World Health Organization, mainly because other issues - most notably the HIV pandemic - have claimed public health attention and dollars.

"But now that is changing," she said, "especially with the tangible effect of actually having the virus circulating in these countries."

Africa was the latest to be hit with avian flu. Of the nine affected nations, three - Nigeria, Egypt, and Djibouti - had a total of 38 human cases last year, with 16 deaths, she said.

But Dr. Chungong said that African public health systems are so unprepared for flu surveillance that no one can tell whether that total is accurate. "It's impossible to be certain," she said.

But millions of Africans, she said, are in regular contact with live poultry. It's the custom to handle chickens in the market before buying, slaughtering is often done at home, and feathers and offal are disposed of casually without regard to safety, she said.

Also, "poultry are practically living in some households."

Those social factors, combined with poor public health facilities, make preparing for a pandemic an "enormous challenge" for Africa, she said.

Dr. Fukuda argued that because of the public-private nature of the flu vaccine development process intellectual property issue - including the patenting of viral strains or development processes - is becoming an important issue.

So far, he said, there's no sign that patent disputes have slowed research.