holds promise of vaccine
For Drs. Dennis Brown and Raquel Hernandez, it was scientific serendipity: a rare “A-ha!” moment with implications for preventing such deadly mosquito-borne diseases as dengue fever and West Nile encephalitis.
Brown and Hernandez, a husband-and-wife team in the College of Agriculture and Life Sciences’ Department of Molecular and Structural Biochemistry, had studied the Sindbis virus for decades. Their goal: to create a three-dimensional image of the virus’ structure, atom by atom, and, thus, give scientists a new way of understanding how that structure influences the way the virus infects both insects and mammals.
Theirs was research at its most basic until Hernandez created a surprising Sindbis mutant. To study interaction among virus proteins, she removed a piece of protein from the virus. She found that while the resulting mutant survived in animal cells, it didn’t reproduce rapidly the way a normal virus would. In insect cells, something different happened: The mutant reproduced at the same rate as the wild virus.
“It became suddenly obvious,” Brown says, that their discovery could pave the way to vaccines for 600 or 700 disease-causing viruses that are spread by mosquitoes and other blood-sucking insects.
Brown and Hernandez speculated that, by injecting people and animals with mutants missing a protein segment, they could impart immunity to the wild virus without triggering illness. Early tests with mice proved they were right, and the researchers have patented their discovery.
To see if what they found with the harmless Sindbis virus holds true with other mosquito-vectored viruses, Brown and Hernandez are collaborating with colleagues from Louisiana State University and the University of Texas Medical Branch in Galveston. In the viruses that cause dengue fever and West Nile encephalitis, they are removing the same protein domain that they took out of Sindbis.
Such tests, they say, will expand the proof of concept from Sindbis to other alphaviruses and the flaviviruses, including those that cause yellow and dengue fevers.
The researchers have focused on Sindbis because it’s faster-growing and easier to work with than other intractable — and harmful — arthropod-vectored viruses, Hernandez says.
Brown says, “It’s an excellent model for learning about membrane-containing viruses because it causes no diseases. You can bathe in it.”
Having contracted a severe laboratory case of dengue fever years ago, Brown knows firsthand of the need for research into potential vaccines. According to a World Health Organization report issued in 2002, dengue fever has reached epidemic proportions, causing 50 million infections and more than 12,000 deaths — mainly among children — each year.
Moreover, the incidence and severity of dengue has risen rapidly since the 1970s. Without a vaccine to prevent the disease, public health officials have relied on mosquito control efforts that have, thus far, failed to control the epidemic.
And while Brown and Hernandez can cite similarly daunting figures for other mosquito-borne viruses, they also recount how frustratingly difficult it is to find investors or drug companies willing to risk the millions of dollars needed to develop a vaccine that would mainly be used in the developing world.
“We have found that the driving force is profits,” Brown says, “and the diseases we are looking at are mainly diseases of poor countries, so the potential for profit is limited.”
Still, Brown and Hernandez continue to make the kind of contacts with benevolent organizations that they believe will one day move their discovery from the laboratory into medical clinics around the world.
“When you
are doing basic research, 99 percent of the time, you never see the
relevance come,” Brown said. “This is one of the rare incidents
where it came out that way, and it’s kind of cool.”
—Dee
Shore
