This week's news that researchers have successfully tested a vaccine for avian flu may have left some with the impression that the danger of a pandemic has all but disappeared. But scientists, public health authorities and drug manufacturers say they still have many challenges to overcome before that's the case.
"There has been a misunderstanding" among those who assume they'll be able to get an avian flu shot soon, said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, who announced the test results last weekend. "We're not going to be deploying the vaccine" immediately, he said.
One reason, he explained, is a chance that the virus, which has spread from birds to at least 112 people since late 2003, is at an evolutionary dead end, and will never mutate into the raging, human-to-human threat that public health officials fear. And if it does mutate, there's no guarantee that today's vaccine will work.
Even so, many authorities are worried because 57 of those who contracted avian flu have died, mostly in Thailand and Vietnam. Officials are preparing as though the virus is the heir apparent to the 1918 international flu pandemic, which killed more than 40 million.
Worldwide, clinical trials of various avian flu vaccine formulations are under way or planned, while governments are stockpiling antiviral drugs that have shown promise in treating patients after they come down with the disease.
In the United States, the government will try to determine whether the vaccine tested on healthy adults at three U.S. sites (including the University of Maryland School of Medicine in Baltimore) is safe and effective for children and patients 65 and older. They are traditionally the most vulnerable groups in a flu outbreak. Those tests should begin within months, Fauci said. The UM Medical School expects to be a test site for both senior citizens and children.
Tests on volunteers who have already received the vaccine - made with a killed virus - showed antibodies that would likely protect them from the live A(H5N1) virus.
Another issue is how much vaccine manufacturers can make and how soon. Experts say current factories can't make nearly enough for this country alone, much less the world. This is particularly true at the high dosage levels that scientists found most effective in tests in Baltimore, Los Angeles and Rochester, N.Y.
So scientists are working on ways to stretch supplies, most likely by adding a chemical to the vaccine or changing how the shot is administered. Governments will also have to decide whether to stockpile the vaccine or distribute it in anticipation of an outbreak - and, if so, to whom it should go first.
"I think the biggest hurdle has to do with making the decision about whether to go ahead with a vaccination campaign," said Dr. John Treanor, a University of Rochester infectious disease specialist who oversaw the trial at his institution. "That has to do with how imminent the threat of pandemic is."
Currently, the U.S. government is in no position to give avian flu vaccine to anyone. It has stockpiled only 2 million doses of the drug used in the trial, which was made by Sanofi Pasteur of Swiftwater, Pa.
But even that supply is in a bulk concentrated form. It can't be finished, packaged and administered until the government tells the company how much antigen should go in each dose, according to Sanofi spokesman Len Lavenda.
David Webster, a Bethlehem, Pa., consultant to vaccine and pharmaceutical companies, estimated the total capacity of flu vaccine manufacturers who supply the U.S. market at only 100 million doses - about a third of the U.S. population.
Sanofi, the biggest supplier of U.S. seasonal flu vaccine, with 60 million doses planned for this season, has broken ground on a new Swiftwater plant that could more than double its capacity by sometime in 2008.
The company has only just begun - with the help of a $97 million government grant - to accelerate plans for a U.S. plant that would use faster production techniques.
Other large manufacturers have plants based overseas and are less likely to make much avian flu vaccine for the U.S. market, Webster said.
The shortage of manufacturing capacity is one reason researchers are immediately turning their attention to stretching the vaccine further.
One technique is to add a chemical that helps stimulate immune responses. When the compound - such as aluminum phosphate - gloms onto the flu antigen, the body's immune system processes it more efficiently, Treanor said.
Another possibility, according to Fauci, is to experiment with injecting the vaccine under the skin rather than into muscle, a technique that requires less vaccine but demands more skill.
A third possibility is spreading the vaccination over three doses rather than two, requiring less of the antigen in each, said Dr. James Campbell, the UM pediatrician who oversaw tests in Baltimore.
But, he said, "The capacity to make it, even at lower doses. ... is just not there. Either it's not given to everyone, or a way of dose-sparing or a new method of production has to occur where you could make it for the entire population."
Meanwhile, some governments are stockpiling the antiviral drug oseltamivir, planning to give it to unvaccinated people in the event of an avian flu outbreak.
The drug, which Roche markets under the brand name Tamiflu, has already been purchased by governments in Hong Kong, Thailand, Singapore, Malaysia and Korea, according to commentary in this week's issue of the journal Lancet.
But even that strategy is subject to second-guessing. The Lancet commentary, by the University of Hong Kong's Kenneth Tsang, suggests that zanamivir, an inhaled antiviral drug, is just about as effective, with fewer side effects. The German government has just purchased 1.7 million doses of that drug, marketed by GlaxoSmithKline as Relenza.