Tick saliva genes key to Lyme disease vaccine

April 08, 2002

KINGSTON, R.I. - April 8, 2002 - When a deer tick bites a human or other mammalian host, it takes more than 24 hours before the Lyme disease bacterium travels from the tick's gut to the tick's salivary glands and then into the host. During that time, bioactive proteins in the tick's saliva begin to suppress the mammal's pain response, increase blood flow to the area, and prevent clotting while at the same time battling the mammal's immune system response to the biting arthropod.

Two University of Rhode Island researchers believe that the proteins in the tick's saliva may be the key to developing a new vaccine for preventing Lyme disease and other tick-transmitted infections by protecting hosts against blood-feeding ticks. The National Institutes of Health recently awarded them $2.3 million to screen for the most promising tick salivary genes over the next five years. URI entomology Professor Thomas Mather and microbiology Professor David Nelson, director and associate director, respectively, of the URI Center for Vector Borne Disease, discovered the importance of tick saliva as a result of NIH-funded research in the late 1990s. The new grant will help them pinpoint the genes and proteins that can best be developed into a vaccine.

"Ticks have more than 400 proteins in their saliva, many of which have evolved to help them steal blood from a host animal by inactivating specific factors of the immune system," explained Mather. "We're attempting to identify, purify, and learn the function of these various proteins, because by disrupting their function we may be able to prevent ticks from feeding and transmitting disease-causing microbes."

Since they began studying the properties of tick saliva in 1994, Mather and Nelson, along with collaborators at NIH, have already identified a significant number of genes that appear promising. More recently their work has focused on developing a system for rapidly screening additional gene candidates for those that might be effective antigens. Mather's research team makes ticks drool into capillary tubes by administering a muscle relaxant to the ticks. A precious commodity, the team has collected more tick saliva than any other researchers in the world.

"That saliva has become a real treasure chest of potent molecules for us," Mather said. "It's now just a matter of sorting them out, which to me is very exciting."

While Mather focuses on the proteins in the tick saliva, Nelson is studying the Lyme disease bacterium itself.

"When the bacterium is in the tick's saliva - on its way from the tick's gut to the mammal host's blood - it's in a starvation mode because there aren't enough nutrients in the tick's saliva for it to grow," said Nelson. "We think we'll be able to find a good vaccine candidate among the genes expressed in the bacterium's physiological response to starvation."

According to Nelson, the Lyme disease bacterium has about 1,000 genes, but he already knows that some aren't good candidates for a vaccine. "To screen all of them isn't a trivial task. But we can predict which should be screened, so we'll probably only need to look at between 75 and 150."

Once Mather and Nelson identify the best vaccine candidates - either in the tick saliva or in the Lyme disease bacterium - they anticipate a pharmaceutical company will complete the process of developing it into a vaccine.
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University of Rhode Island

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