Avian Flu Vaccine Offers Hope Coupled With Questions

It seems effective, but immunity requires 2 shots and longer time to take effect, researchers say

TUESDAY, Oct. 11, 2005 (HealthDay News) -- While initial testing of an avian flu vaccine shows promise and trials should be completed by the end of the year, questions remain about the vaccine's ability to protect large numbers of people, U.S. researchers say.

Among the potential problems: The vaccine dose needs to be much higher than that given for other types of flu, according to Dr. John Treanor, a professor of medicine and associate professor of microbiology and immunology at the University of Rochester School of Medicine and Dentistry.

"It seems to be a characteristic of the H5 vaccines that they require a higher dose to illicit an immune response than some other vaccines do. Dose-related immune responses are being tested to get a feeling for what dose would be required. And then we need to see if anything could be done so lower doses could be used," said Treanor, who is the principal investigator of the vaccine tests being done at the University of Rochester.

The trials, under the auspices of the U.S. Department of Health and Human Services, are also being conducted at the University of Maryland School of Medicine and the University of California, Los Angeles.

The initial trial, done on healthy adults, produced a strong immune response in 113 of the 452 participants in the study. All the participants were healthy adults under the age of 65. The next step is to test the vaccine on people over 65 and children.

The problems with a high-dose H5 vaccine are twofold:

First, since people have never been exposed to H5 viruses, a "primer" vaccination would have to be given, then a month later another dose would be required. Because of this two-dose regimen, immunity wouldn't take hold for about six weeks, giving the virus a bigger window to infect even immunized individuals, Treanor said.

Second, the higher dose would place a strain on manufacturers' ability to produce enough vaccine, he said.

It's also not known if the vaccine being tested now would protect against an H5 virus strain that might trigger a flu pandemic.

"So far, the viruses that have been isolated from people have all been very similar to each other," Treanor said. "The vaccines that have been made would be expected to protect quite well against all the different viruses that have been isolated from people."

In the past two years, the H5N1 strain of avian flu has infected poultry throughout Southeast Asia, prompting health officials to order the destruction of millions of birds to prevent the virus' spread to people. So far, human infections have been limited, with an estimated 65 deaths, most of them in Vietnam.

But the virus is moving westward. On Monday, Turkish and Romanian officials slaughtered thousands of domestic fowl after the disease was detected in birds. The European Union and other countries have banned the import of poultry from those two countries, according to the Associated Press.

The U.S. Department of Health and Human Service has contracted with the drug maker Sanofi Pasteur to produce $100 million dollars worth of the avian flu vaccine being tested now.

Because the vaccine requires two doses and the most effective dose isn't yet known, it's not clear how many doses $100 million would buy. "It's not yet certain what the formulation of the vaccine will be," said Sanofi Pasteur spokesman Len Lavenda. "We don't know the concentration of antigen that is required to illicit a full immune response."

Lavenda said further study is needed to determine how much vaccine is required for each dose. "We are producing this vaccine in a bulk concentrated form," he said. "Once we get an answer about concentration, we will be able to answer the question about how many doses it would yield."

The good news is the current strain of avian flu -- called H5N1 -- hasn't shown the ability to pass easily from person to person. But experts worry this could change if the virus mutates.

And if the virus were to mutate, making human transmission far easier, it's not known if the U.S. vaccine under review would be effective, Treanor said.

"The kinds of mutations that might be responsible for person-to-person transmission could have nothing at all to do with what determines the agnogenic reaction," he said. "It is impossible to say if that would require a significant change in the vaccine or not."

Once a vaccine is approved, it would take six to eight months before a substantial supply could be made available, Treanor added. Currently, there are only 2 million doses of the experimental vaccine on hand.

Among the strategies being weighed to combat a potential pandemic are making large amounts of the vaccine under review and then stockpiling it, before vaccinating people in anticipation of a pandemic. "But is it really too early to go ahead now when we don't know for sure what virus might emerge, or even how likely it is that this is going to turn into a problem?" Treanor asked.

While world and U.S. health officials have been warning for months that the avian flu strain sweeping through Asia could trigger the next pandemic, some scientists are saying it probably doesn't pose an immediate threat.

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, told The New York Times on Sunday that a pandemic was not likely for the coming flu season. "How unlikely, I can't quantitate it," Fauci said. But, "you must prepare for the worst-case scenario. To do anything less would be irresponsible."

And Dr. Jeffery Taubenberger, chief of the molecular pathology department at the Armed Forces Institute of Pathology, in Washington, D.C., told the newspaper: "I would not say it's [a pandemic] imminent or inevitable. I think in the future there will be a pandemic." But, he continued, whether that pandemic will be avian flu or another type of flu is impossible to predict at this point.

Dr. James D. Campbell is an assistant professor of pediatrics at the Center for Vaccine Development at the University of Maryland, and is leading the avian flu vaccine research at that school.

He said the vaccine appears to be safe. "Over the last six months, there have been no surprises in terms of safety. Essentially, the safety profile seems to be the same as regular flu vaccine," he said.

He said it might be possible to reduce the number of shots needed by including substances, called adjuvants, in the vaccine that boost the immune system's response, Campbell said. "When adjuvants are used in avian flu vaccines, they seem to work better than without adjuvants," he said. "This is being looked into."

Other strategies for getting people vaccinated are to add the avian flu vaccine to current flu vaccines, Campbell said. "We don't know if the epidemic is coming this year, or the year after," he said. "If people were primed, even if it were with a single shot, potentially, it might only take one shot at the time the pandemic came."

More information

The U.S. Centers for Disease Control and Prevention can tell you more about avian flu.

SOURCES: John Treanor, M.D., professor, medicine, and associate professor, microbiology and immunology, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; James D. Campbell, M.D., assistant professor, pediatrics, Center for Vaccine Development, University of Maryland, Baltimore
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