Vaccine Hunters

Chikungunya and dengue fever are two mosquito-carried viruses that threaten almost three billion people worldwide. Both illnesses cause serious flu-like symptoms, and dengue fever can be fatal. A Raleigh biotech start-up is using technology from NC State in its race to create a vaccine to stop the spread of the viruses.

RALEIGH — At first glance, the labs at Raleigh biotech start-up Arbovax look pretty standard. Researchers in white lab coats transferring fluids from vials and test tubes, scientific instruments, scales, glass screens over work areas, and the list goes on.

But when you see the danger signs at various points around the lab, you quickly realize the viruses being studied here are the not your usual, run-of-the-mill viruses.

“These viruses are pretty unique in the virus world,” explains Malcolm Thomas, President and CEO of Arbovax. “They can grow in two phylogenetically different hosts, which are insects and mammals.”

In this case, those words “insects and mammals” really mean mosquitoes and humans. And in the case of these viruses, mosquitoes can transmit the virus to people through a single bite. There are about 200 mosquito-borne viruses, but there are two specific illnesses the scientists at Arobovax are concerned with: dengue fever and chikungunya.

It doesn’t take much for a mosquito-borne virus to spread. It only takes one mosquito to bite one person, one time, to transmit the disease. But if several mosquitoes then bite that person, the insects are able to transmit the disease to more people. That cascading effect can spread the disease rapidly.

And that’s what is happening right now. 

Dengue fever and chikungunya have devastated developing countries. Both viruses cause debilitating flu-like symptoms, and dengue fever can be fatal. 

But because more and more people are traveling for work, vacation, and even volunteer service opportunities, the disease is spreading beyond the developing world. Infected people are bringing the illnesses from developing countries into the industrialized world and getting bitten by mosquitoes, which then spread the virus to others. The Centers for Disease Control and Prevention reports cases of both illnesses have been found in the United States. Health officials say almost three billion people, roughly 40% of the world’s population, is at risk, yet there are no vaccines that offer protection.

But that may be changing. And with the diseases spreading, the development of a vaccine couldn’t come at a better time.

Researchers at Arbovax, using technology from North Carolina State University, say they have discovered a vaccine. By studying the virus’ DNA, researchers found several important elements required by the cell to replicate. By removing those parts of the genome, scientists interrupt the life cycle of the virus, so that it grows normally in the mosquito but it can’t grow in a person.

That mutated virus can be used as a vaccine.

“The vaccine is actually a virus that has been modified to grow in the insect cell but is severely attenuated, or unable to grow, in the mammalian cell,” explains Thomas. “Although it is challenging in practice, it’s an elegant, very simple concept. It is also a very powerful concept because it seems to work across all of the species.”

Like many groundbreaking scientific discoveries, the concept for the vaccine stemmed from a radical idea, born out of a lifetime of studying viruses.

“Our hypothesis was that these were insect viruses that had expanded their host range to include vertebrates over millions of years,” says Dr. Dennis Brown, Professor of Biochemistry at North Carolina State University and one of the founders of Arbovax. “And to make that leap, they developed certain genetic elements to adapt, live, and replicate in these new organisms.”

The goal of the research was to identify those elements needed to adapt to the new organisms and selectively remove them. That reverted the virus back to being an insect virus. So while the virus can live and replicate in an insect, it can’t copy itself in a human.

“It’s exciting but it is also a high anxiety sort of thing,” adds Dr. Brown. “We are on the verge of doing something out of basic science that has real medical relevance.”

“What makes it even more exciting is that we had a hypothesis and it turned out to be correct,” says Dr. Raquel Hernandez, who helped in the discovery, along with her husband Dr. Brown. “And you watch that hypothesis work first in mice, then in monkeys and we will soon see it in humans. It’s a special feeling.”

With its testing of the new vaccine complete, Arbovax is looking for financial backers to manufacture enough vaccine to begin human trials. If all goes well, a vaccine could be ready for sale and use within three years.

“There’s no therapy for any of these illnesses, and because they are all viral diseases, a vaccine is the only way to go,” says Thomas. “So it’s very important that we develop vaccines for these diseases and, because they are spreading so fast, we need to develop them quickly.”

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