Getting a Jump on the Viral Invaders


Vaccine maker Acambis' hunch in '99 that the disease could be a big problem is paying off. Chief Science Officer Tom Monath talks about how the company is facing the challenge

As Chief Scientific Officer at Acambis (ACAM), Dr. Tom Monath is deeply involved both in the fight against terrorism and the battle against a new threat: the West Nile virus and other emerging diseases (See BW Online, 8/9/02, "A New Breed of Microbe Hunters"). BusinessWeek Online reporter David Shook recently spoke with Monath. Edited excerpts of their conversation follow.

Q: How did you know back in 1999 that West Nile virus might become a recurring problem in the U.S.?

A: It was a bit speculative on our part, but after the epidemic in '99, we predicted it might come to this. We submitted for a grant to look into a vaccine for it from the National Institutes of Health. We were awarded $3 million [in August, 2000] and immediately put that project into high gear. At the time, many people wondered what we were doing, but now there's a lot of interest and envy in our project.

Q: Acambis is a small company in the private sector, but the projects you've been working on are decidedly public-health initiatives -- vaccines for the masses. How will that pay off for a private biotech company?

A: When we first started some of these vaccine projects, there were a lot of uncertainties about the future of epidemiology and the market for some of these vaccines. But we've developed a technology platform, ChimeriVax, that allows us to construct vaccines against many very serious problems around the world, like Japanese encephalitis and dengue fever.

For those diseases, there is a clear market -- a huge demand. For the West Nile program, yes, to some extent, it does involve looking into a crystal ball to see what will happen in the U.S. from this point. But if you look at what has taken place so far, it looks like a truly emerging disease. Because mosquitoes that carry the virus and birds that are often infected by it are so influenced by changes in climate and weather patterns, there are so many factors that could spread the disease in ways we don't fully understand yet.

We do feel that these mosquito-borne diseases will occur with varying intensity from one year to the next. We might see Chicago with thousands of cases of West Nile infections one year, but no epidemic the next year.

This is never going to be a measles vaccine -- one where every child is immunized. But we do see a substantial market for this vaccine.

Q: How does ChimeriVax work?

A: The idea is to use an old friend, the yellow-fever vaccine [which has been used since the 1930s]. We started with that vaccine and removed the gene that codes for the structural proteins of the virus.

Think of a virus as a bag of nucleic acid that has an envelope or coat that protects it from the environment. That envelope contains antigens which your body responds to, creating an immune response. We replace that coat with that of the West Nile virus [for example]. But the bag inside is still the nucleic acid of the attenuated yellow fever virus, which causes a completely asymptomatic response, a very mild infection. The body then recognizes West Nile and creates an immune response without actually being infected by the West Nile virus.

Q: So the principle behind ChimeriVax is you use a live virus, but a weakened, genetically altered form of one?

A: Yes. All the best vaccines are live viruses because they carry the ability to replicate in the body. The immune response to a live viral vaccine is much greater than if you're using a killed virus. All the old vaccines for polio, measles, and mumps are weakened forms of a live virus.

Q: What is the status of the West Nile vaccine?

A: The data so far have knocked our socks off. Right now all we have is data from trials in monkeys. But the data look terrific. We'll begin human trials probably in the first quarter of next year.

Q: Can you tell me anything about the smallpox vaccine you're developing for the federal government?

A: We have a contract to deliver 209 million doses by the end of the year. That program is moving along well. There is somewhat of a gag order on the specifics about this, but I can say that the vaccine is made using modern methods. It's a new vaccine but is derived from the old one. We are, in effect, purifying the vaccinia virus used in the 20th century. [The purification may eliminate some of the rare side effects of smallpox virus, such as fever.]

The idea is to develop a vaccine that matches the old one in all of its clinical properties. That way, we can reasonably assume that it works because the old vaccine worked so well. But of course, there's no way to test it. Smallpox doesn't exist in nature anymore.

Q: So right now, most of your revenue is coming from the government contract for a smallpox vaccine, worth more than $428 million over several years. But your real emphasis is on other viral tropical diseases that actually are causing problems in all corners of the world. Why?

A: There are 500 million people in the world traveling each year. There are 27 million Americans going to tropical areas annually. There's a huge demand to protect against these kinds of infections. Japanese encephalitis and dengue fever are two of the more virulent infections American travelers can get.

And we're not just talking about developing a travel vaccine for affluent people. For ethical reasons, we want to make sure that any new promising product is available to the developing world. We understand that many countries will be unable to pay for it. It does get complicated in thinking about the economics of these vaccines. But right now we're focused on developing them.


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