Dennis Brown and Raquel Hernandez, a husband-and-wife research team at N.C. State University, have turned a miscalculation 14 years ago into a new way to fight insect-borne diseases.

Now the couple hope that Arbovax, the tiny Raleigh biotech that Brown co-founded, can turn their discovery into vaccines.

To succeed, they'll need investors and partners and another four to eight years.

Those might seem like large obstacles, but the Triangle market looks favorably on its research scientists. The region is also home to Novartis, Merck and GlaxoSmithKline, three of a handful of global companies that make vaccines.

And Arbovax's timing is spot-on.

Rising fear that insect-borne diseases will spread beyond the tropics is boosting efforts in this country and Europe to develop vaccines. Experts blame global warming and an increase in international travel and commerce for the growing threat of such diseases as dengue fever, West Nile and chikungunya, a debilitating illness that is similar to the other two.

Few effective treatments for insect-borne viral diseases exist, and the need to prevent infection is large, especially for dengue fever. Every year, an estimated 100 million people worldwide contract dengue fever, according to the Centers for Disease Control and Prevention in Atlanta. In 1 percent of cases, the infections are fatal.

The dengue virus, which is transmitted by mosquitoes, has become more virulent and widespread in the past 50 years.

Researchers worry that an increasing number of travelers and military personnel will allow the virus to enter the Southeastern United States, where a possible carrier, the Asian tiger mosquito, has become plentiful in the past two decades.

The Asian tiger mosquito is also a carrier of the chikungunya virus, which has caused epidemics in Africa and Asia. Last year, the first cases were reported in Italy, according to research magazine Science.

Worried about the U.S.

There's no reason why chikungunya couldn't spread across Europe and to this country, Ann Powers, a CDC expert, told the magazine.

The West Nile virus, also transmitted by infected mosquitoes, arrived in the United States about a decade ago and has spread to almost every state, according to the CDC.

In 2006, nearly 4,300 U.S. cases were reported; 177 of them were fatal.

Vaccines for these and other insect-borne diseases could generate more than $1 billion in annual sales worldwide, estimated Malcolm Thomas, Arbovax's chief executive.

Big discovery made

The discovery that Brown and Hernandez, his collaborator of 15 years, made in the early 1990s could be a way to tap that market, Thomas said.

The couple's "aha" moment took them by surprise.

"It was one of these things you felt a little bit foolish about, because you should have thought of it years ago," Brown said.

They were working with viruses for the independent Research Development Foundation in Houston. In their experiments, they were using viruses in which the tails had been partly clipped.

They knew the viruses wouldn't multiply rapidly and cause a full-blown infection in mammalian cells. They thought the same was true for insect cells.

Then Brown suggested testing that assumption, Hernandez said.

His idea and her hands-on ability led to an experiment that proved them wrong. They found that viruses with clipped tails multiplied as rapidly in insect cells as viruses with intact tails.

That opened the possibility of using insect cells to grow viruses that promise to not only be harmless in humans, horses, livestock and other mammals but also produce a comprehensive immune response that protects from infection.

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