SAN JOSE, Calif. – On the hunt for a vaccine against bird flu, biotech companies are coming up with leads on something even better: a universal vaccine that works against all kinds of flu.

Some claim it’s possible the bird-flu medicines they are developing could also provide improved treatments for the common winter flu and even allow people to get flu shots only once every few years.

Experts caution that much still needs to be done. But some claim to have found ways to boost flu vaccine potency by using special additives. Others have devised methods to manufacture medicines quickly in an emergency and to tackle the problem of the virus mutating into drug-resistant forms.

Since the bird-flu virus took its first human life in Hong Kong in 1997, it has killed a relatively small number of people – 151 people in 10 countries – compared with the 36,000 people killed annually by the common flu in this country alone. Still, many experts believe bird flu will inevitably develop into a form that could spread across the globe in a so-called pandemic that could leave many millions dead.

“Someday there will be a pandemic flu,” said Anthony Fauci, head of the federal government’s National Institute for Allergy and Infectious Diseases. “Sooner or later, we’re going to get it.”

At least 28 bird-flu vaccines are under development by 13 different companies worldwide, according to the International Federation of Pharmaceutical Manufacturers & Associations. One of the most intriguing of these new medicines is a so-called universal vaccine, which some people believe could be useful against various strains of bird flu as well as seasonal flu.

Drug companies typically design their seasonal flu vaccines to generate antibodies that neutralize two proteins, hemagglutinin and neuraminidase, on flu viruses. But because these two proteins are prone to mutate, new vaccines tailored to their changing characteristics usually have to be made every year.

That variability could prove devastating if the bird-flu virus suddenly mutates into a form that spreads quickly among people instead of just birds. By the time vaccines could be manufactured to target the new virus, thousands of people could die.

However, scientists at Dynavax Technologies in Berkeley, Calif., believe they have found a possible solution. They have developed a vaccine that targets two other common flu proteins, the nucleoprotein and matrix protein, which tend to remain stable. That way, even if some bird-flu virus proteins mutate, Dynavax scientists say, their vaccine still would be effective against the proteins that don’t change.

Like most other drugs in the works to counter bird flu, the Dynavax vaccine is in an early stage of development. But on Oct. 20, the company presented data at the Second International Conference on Influenza Vaccines for the World in Vienna that showed it was effective in mice and baboons.

If it also proves effective in people, it could be used for bird flu or seasonal flu, said Gary Van Nest, Dynavax’s vice president of preclinical research. Moreover, because the vaccine presumably would work no matter how the flu virus mutates, one shot of it every three years or so might be sufficient to protect a person, he said.

As an added safeguard, however, Dynavax plans to give its vaccine to people along with a standard vaccine that targets the mutating proteins.

“The best approach is to combine it with what we know works pretty well and make it work very well,” Van Nest said.

Scientists at Vical in San Diego have reported progress with a similar vaccine. And researchers at the University of Bath in England are trying to develop mutation-resistant versions of anti-viral drugs – such as Tamiflu, developed by Gilead Sciences – which would be used to treat people already infected with bird flu.

Another big problem vaccine manufacturers face with bird flu is its novelty.

Because most people have been exposed to the seasonal flu virus at some time in their lives, they have developed some built-in immunity to it. But because bird flu is new, no such previously developed immunity exists.

Consequently, unless some way can be found to boost people’s immune systems, health officials fear people would need relatively large amounts of bird-flu vaccine. That could require huge stockpiles of the vaccine and perhaps force people to get more than one shot.

So a number of companies including Novartis – which acquired Chiron and its Emeryville, Calif., vaccine research facilities earlier this year – are adding boosters called adjuvants to their bird-flu vaccines. Made of water and shark liver oil, Novartis’ booster “kind of gets the body riled up a little more so the immune response is better,” said company spokeswoman Alison Marquiss.

Even with boosters, some bird-flu vaccines tested so far require high doses to get an adequate immune response. But in July, GlaxoSmithKline of England announced that its adjuvant-boosted vaccine triggered a strong immune reaction in about 80 percent of 400 people who received it in a study.

Yet another concern is how to manufacture enough doses of bird-flu vaccine quickly for the billions of people around the world who might need it. The typical method of making flu vaccines, which partly involve growing the virus in fertilized chicken eggs, has serious drawbacks.

If a bird-flu outbreak occurred, vaccine manufacturers would have to obtain millions of eggs on short notice. But the virus could kill many of the chickens counted on to produce those eggs. Moreover, manufacturers can’t just snap their fingers to bolster their egg supplies, said George Kemble, vice president of vaccine research & development for MedImmune of Maryland. MedImmune is working on potential bird-flu drugs at its California facilities.

“If we want to increase the number of eggs, we have to tell the farmers many months in advance,” he said.

To avoid that problem, federal authorities in May awarded the Bay Area operations of Novartis and MedImmune a total of nearly $400 million over next five years to make vaccines from a process using mammal cell cultures.

The ingredients for such cultures can be stored in freezers and be instantly available in the event of a health emergency. They also tend to be less bulky than eggs. As a result, scientists can make vaccines more quickly with cells than with eggs, Kemble said.

Cell-based vaccines also seem to work as well as those derived from eggs, according to data Novartis presented Oct. 19 at the Vienna flu conference. In a study involving more than 2,600 people, in which some were given a cell-based seasonal flu vaccine and others an egg-based version, Novartis said it found no difference in their immune responses.

As promising as such developments are, however, the world would be woefully unprepared if a bird-flu outbreak were to occur in the near future, health authorities warn.

Even if companies significantly expanded their manufacturing operations over the next three years and ran their production lines 24 hours a day, it wouldn’t be sufficient to meet the threat, according to a study in September by the World Health Organization.

“If an influenza pandemic were to occur,” the study concluded, “the potential vaccine supply would fall several billion doses short of the amount needed to provide protection to the global population.”

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