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Feds Race to Make SARS Vaccine

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01:09 PM May. 28, 2003 PT

Fifteen or 20 years to create a new vaccine is considered quite speedy. So the federal government's blueprint for a shot to stop the SARS epidemic in a mere three years seems positively head-snapping.

Can it be done?

Certainly, says Dr. Gary Nabel, chief of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. "If everything went perfectly," he qualifies. "If all the stars were aligned."

The stars almost never align precisely in medical research. But if they do, Nabel says scientists will finish all the basic lab work, creating the vaccine and testing it in animals, in just one year.

Then they will spend two more trying it out on people to make sure it works, turn the results over to the Food and Drug Administration and be done.

No vaccine in modern times has gone from start to finish nearly that fast. But even if Nabel's time line proves unrealistic, his willingness to state it out loud shows how seriously the government takes SARS.

The strategy for changing the pace from glacial to galactic: Forget solving problems one at a time.

At Nabel's institute, two teams are working separately to create possible vaccines. One sticks to the time-tested approach of making them with dead or weakened viruses. The other builds them with up-to-the-second gene-splicing tools.

Instead of dealing with big technical issues in the usual one-by-one order, scientists will jump into all of them at once. For instance, they are gearing up production of newly minted vaccines at the same time they figure out how to test them in animals and tease apart exactly how the human immune system does the job of fighting off SARS on its own.

"Parallel tracking," Nabel calls this. It's also called science in a hurry.

Why the rush? Why work so hard to defend against a disease that is just a few months old, that has yet to kill a single person in the United States?

No one knows how bad SARS will become, whether it will burn out or continue to spread, even exactly how it makes people so sick. But the consensus among the country's top health officials is that it would be foolish to wait and see.

Even if SARS is somehow contained in China and Taiwan, many experts doubt it will ever be wiped from the planet, even though this is the World Health Organization's goal. More likely, they say, the virus will come and go, perhaps in some seasonal pattern, maybe by chance.

No matter what happens in the next few months, federal officials promise to keep working on a vaccine so the world will be ready whenever, wherever SARS returns.

"We need a vaccine. There's no question about it," says Dr. Anthony Fauci, head of the infectious disease institute. "This is potentially disastrous enough that we can't just hope it will go away and stay away."

The government is not alone in this. It is encouraging private vaccine makers to take a crack at SARS. In April, Health and Human Services Secretary Tommy Thompson hosted a meeting of vaccine scientists, where government researchers shared what they knew about the virus and promised them samples to work with.

"They more or less said, 'We want your entrepreneurial brains working on this,"' says Una Ryan, president of Avant Immunotherapeutics.

Labs from Hong Kong to Canada are also tackling SARS vaccines, and Fauci said his institute will sign contracts with up to a dozen companies to help with development.

At this point, however, the single biggest question is still unanswered: Is a SARS vaccine even possible?

Dr. Emilio Emini, head of vaccine development at Merck, is among those trying to answer this. For now he refuses even to chance a guess.

"This is a new virus. So much is not understood," he says. "It's a big black box."

Still, Nabel says he knows of at least three major pharmaceutical companies besides Merck, the world's largest vaccine maker, that have gone to work on SARS, even though no one can be sure whether there will ever be a market for a vaccine.

Their success will depend on figuring out a way to train the body's immune system to see the SARS virus quickly, to recognize it as dangerous and to kill it before it makes people sick.

Even as well as this approach has subdued some of the world's most persistent infections, there are many notable exceptions. Malaria and tuberculosis, for instance, have resisted decades of vaccine research. And of course scientists cannot forget their humbling failure at a vaccine for HIV, the most studied virus in history.

Nevertheless, one strong clue at least gives them some hope: Most people who catch the SARS virus eventually fight it off and get better.

"That means their immune response is working, and that means a vaccine is possible," says Dr. Louis Picker, associate director of Oregon Health & Science University's Vaccine and Gene Therapy Institute. "It's just a matter of finding the approach that will mimic that response without being too dangerous."

Worry that a vaccine will be too dangerous is one reason development takes so long. No one wants to make healthy people sick by giving them shots intended to prevent illness. So typically vaccines are tested painstakingly on thousands of volunteers over many years to prove they do far more good than harm.

Even with this, dangers may come to light only when they get into routine use. Four years ago, the first rotavirus vaccine was pulled from the market after just one year. The shots prevent childhood diarrhea, but they also turned out to cause life-threatening bowel obstructions in one in 10,000 recipients.

Scientists are especially cautious because of their experience with vaccines aimed at animal relatives of the SARS virus. SARS is a coronavirus, the same virus family that causes serious diseases in pigs and other animals. While shots work well against some of these, they occasionally go disastrously bad. A vaccine for the feline coronavirus actually results in worse disease, not less, when cats catch the virus.

Vaccines work by giving the body a glimpse of its target, typically a dead virus, a weakened live one or bits of viral proteins. When all goes well, the immune system remembers these and goes on full attack when it later encounters the real thing.

But as happened with the cat vaccine, they sometimes trigger an off-kilter immune reaction, so when attacked by the actual virus, the system responds with a weak or misguided defense.

Vaccines made from killed viruses can have this paradoxical result. And even if they do no harm, the killed virus vaccines often fail to rally a meaningful counter-assault. Nevertheless, the approach works against some microbes, including the flu, and the infectious disease institute's Dr. Brian Murphy is developing a SARS vaccine with virus killed with formaldehyde.

When that is finished, Murphy will probably turn to another approach that has produced most of the world's vaccines, an attenuated virus. These are made by growing the virus over and over until it builds up enough mutations to leave it too weak to do harm.

Because the attenuated viruses cause true infections, they trigger an especially robust and well-rounded defense, arming the immune system to launch both antibodies and virus-killing T cells. But there are drawbacks: They can take a long time to make, and the crippled virus can theoretically mutate to regain its power, making people sick.

"They are effective but dangerous, and it will take a long time to get one we would give to people," says Picker.

Vaccines based on genetic engineering may be faster.

One approach is using gene-splicing to make plenty of SARS virus parts, such as the protein prongs that stick out from the virus, giving it a crown-like appearance under a microscope. Injecting these proteins -- but not the virus itself -- may be enough to prompt the immune system to recognize the SARS virus.

A vaccine made this way works well against hepatitis B. But like killed viruses, the bare proteins can also trigger wimpy or aberrant immune responses.

Nabel's own lab is taking another gene-based approach -- harmless viruses hollowed out to carry SARS genes into the body. Many such delivery vehicles are possible, but Nabel uses a weakened adenovirus, a bug that ordinarily causes colds, that is fitted out with SARS DNA.

Inside the body, these genes should produce authentic-looking SARS proteins, and researchers hope they stimulate a knockout strike against the SARS virus with the full repertoire of immune system weapons.

Even if one of these approaches quickly shows promise, it still must be pushed through human testing in a part of the world where SARS is spreading or, if SARS disappears, go through extensive animal testing. Some doubt all this can be accomplished quickly.

"Could the rules get changed so it would take less than 15 years? Yes. But could it be three years?" asks Dr. Donna Ambrosino, head of Massachusetts Biologic Laboratory, a nonprofit vaccine maker.

Doubtful, she says. There are simply too many unknowns, both about the virus itself and the safety of any strategy to stop it. She notes that scientists have been trying since the 1960s to make a vaccine for another breathing infection, the respiratory syncytial virus, which causes serious disease in babies.

"We know the proteins. We know the antibodies. We have animal models. We know all of that," she says. "But we still don't have a vaccine that works."

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