Athens, Ga. – Researchers at the University of Georgia have discovered a new way to direct a vaccine to the parasite that causes Chagas disease, a leading cause of death among young to middle-age adults in areas of South America where it is endemic.
Chagas disease is caused by the parasite Trypanosoma cruzi, which spreads via a subspecies of blood-feeding insects commonly known as “kissing bugs” because they tend to bite people on the face and lips. While the disease can progress slowly, chronic infection almost inevitably results in irreparable damage to heart and digestive system tissues.
“Chagas disease is incredibly understudied, because it is a disease of poverty,” said Rick Tarleton, Distinguished Research Professor in the department of cellular biology in UGA’s Franklin College of Arts and Sciences and co-author of a paper describing their work in Cell Host and Microbe. “I don’t know if we will ever see a Chagas disease vaccine for humans, but our lab is working on a unique vaccine for animals that may ultimately protect people at greatest risk for exposure.”
The paper reported a new vaccine technique that targets antibodies found on T. cruzi’s flagellum, a tail-like appendage similar to those found on sperm cells, which allows the parasite to propel itself through blood as it searches for cells to infect.
Immediately after infection, the flagellum essentially snaps off through a process of cell division. The discarded tail is broken down by the host cell, but it leaves behind a kind of molecular calling card that Tarleton and his co-author, Samarchith Kurup, were able to isolate and use as the foundation for a vaccine.
In laboratory tests, T cells taught to recognize the proteins found on the flagellum were able to detect infected host cells more than 20 hours earlier than is normally observed, suggesting that the immune system became aware of the parasite’s presence very shortly after infection.
“We want to find a way to help the animal’s immune system recognize which cells are infected with the parasite, and the antigens in the flagellum are an attractive target,” Tarleton said. “If we can express these proteins in a vaccine, T cells will go to work and destroy compromised cells before the infection becomes chronic.”
A significant portion of Tarleton’s work in UGA’s Center for Tropical and Emerging Global Diseases has focused on the development of a vaccine that can be administered to domestic animals, which play a major role in Chagas disease transmission throughout much of the Americas.
“The bugs that transmit this disease are found commonly in substandard housing with poor insulation, but the bugs tend to acquire the parasite from the family pet that spends a lot of time outside,” he said. “These are the same bugs that go on to bite people, so if we can prevent animals from acquiring the disease, we can hopefully prevent T. cruzi’s spread into human populations.”
The research team hopes that this latest discovery will become a major component of its vaccine development, which will ultimately target multiple unique signatures created by T. cruzi infection.
“There’s a lot more work to do, but this new target will be very helpful in the fight against Chagas’ disease,” Tarleton said.
For a full version of the paper, see http://www.cell.com/cell-host-microbe/abstract/S1931-3128(14)00336-9
The research discussed in this article was supported by two grants from the National Institutes of Health under project numbers AI108265 and AI108265.