Clock Ticking on Vaccine Options
Printed November 14, 2005 at wired.com

On Oct. 31, the Bush administration introduced a $7.1 billion plan to make a pandemic avian flu vaccine for every American. Great idea. The only problem is that it will take at least five years to create enough manufacturing capacity to reach that goal. Then it will take another eight months to create a new vaccine that combats the specific strain that would be killing people. In other words, it would be 2011 at the earliest before every American could be vaccinated against a bird flu pandemic.

That's not fast enough. "If a pandemic erupts within the next two years, we have nothing in our armament to fight it on a broad scale," says Peter Dunnill, the chairman of the biochemistry engineering department at University College, London, and an expert on the manufacture of vaccines.

That's not to say scientists don't have any short-term options. There are currently several experimental vaccines and treatments that could be pushed through in the case of a sudden pandemic. But to work quickly these options would need significant funding, regulatory haste and preplanning, which unfortunately don't exist in the president's program. If funding should materialize, here are three ideas that might just save the world:

DNA vaccines: Traditional vaccines are grown in chicken eggs, which is tortuously expensive and time-consuming. But several experimental naked DNA vaccines, which consist of pure DNA that would be sprayed into the lungs, could be mass-produced very quickly using well-understood technology. If a massive government-backed testing effort were put into action now, we could have enough DNA vaccine to cover every person on the planet, all for far less than the $7 billion the U.S. government will pay for conventional vaccines and antivirals. And if such production capacity were available, the stockpile could be created in two or three months.

However, DNA vaccines have never been tested in full-blown clinical trial. "The evidence we have makes it appear that they are safe, but the threat is the unknown. We don't want to give people vaccines that might make them more sick than the disease we're trying to prevent," says Dunnill, and DNA vaccines should be used only if the lethality of a pandemic is high. "If one out of a thousand who gets the disease die, it's not worth it to take risks. But if the death rate is 50 percent and billions of people are contracting it, the risk of a DNA vaccine would probably be well worth it." Such a decision can't be made, Dunnill points out, if we don't have the DNA vaccine on hand to begin with.

RNAi: If a vaccine or antiviral drugs aren't available, another option is to silence the virus's genes inside the human cell. A Boston-based biotechnology company called Alnylam Pharmaceuticals already has several potential RNA interference, or RNAi, treatments for H5N1 ready to be tested in humans. And Alnylam's compounds are designed to act against a broad range of flu viruses, so they might be more effective against a rapidly mutating virus.

Again, however, safety is a concern. The RNAi process was discovered in humans only five years ago and no disease treatment has been tested on more than a few dozen human beings. Using such an experimental technique on a massive scale would be very hard to approve, considering all the unknown risks. The good news is that all past studies have shown RNAi to be a transient actor in the human body, meaning it acts by temporarily silencing genes rather than changing a person's genetic makeup.

Vaccine boosters: Vaccines can be diluted dramatically if they have good adjuvants, which are chemicals that are added to vaccines to make them more effective. Thus the 100 million or so doses of traditional H5N1 vaccine that should be ready within a couple of years could be stretched into half a billion doses if combined with super-adjuvants. A host of such adjuvants are exiting laboratories right now to start clinical trials soon, but it will take a decade of such trials to get them to market through the traditional route. A fast-tracked experimental program could have them ready and available within two years.

One such adjuvant, called Ampligen, made by Hemispherx Biopharma, has already finished clinical trials for chronic fatigue syndrome and is currently wending its way through the FDA approval process. Assuming it passes through the FDA's hoops (which isn't a given -- previous Hemispherx efforts at drug development have been criticized by some scientists), extending that approval for avian flu virus might increase our vaccine stockpiles by a factor of three, says William Carter, the company's CEO.

Even more promising, says Carter, is to use Ampligen together with traditional antiviral medications like Tamiflu or Relenza. That would allow doctors to dilute those drugs by a factor of five and still retain efficacy. That would turn our planned stockpile of 44 million Tamiflu treatments into 220 million treatments, without making it a less effective drug. "We can produce 30 million doses a year if it's called for," says Carter. He adds that his company would license the drug to other manufacturers throughout the world to produce more of it on an emergency basis. "This isn't something you can do in your garage," he says, "but compared to most vaccines and pharmaceuticals, it's a relatively simple five-step process."

Dismantling patents: If a pandemic descends quickly, the only frontline defense against it would be to treat sick people with existing antiviral drugs like patented Tamiflu and Relenza. The manufacturers of those drugs, Roche and GlaxoSmithKline, have limited manufacturing capacity. Government authorities, including those in Taiwan and Vietnam, have raised the possibility of breaking patents so they can manufacture supplies for their own populations.

A government-mediated discussion should begin about how to produce such drugs and under what terms the patents should be broken. "Industry and government agree on one thing: Neither wants to deal with this problem until the last minute," says Dunnill. "If we start discussing it now, we can make intelligent decisions when the crisis hits."