Countering a Tsetse Fly's Bite

The bite of a tsetse fly transmits African trypanosomes, single-cell parasites that cause devastating diseases in humans as well as domesticated animals throughout large swaths of Africa.

Strategies used to curtail the spread of these diseases, which rely primarily on reducing the tsetse fly populations with traps and insecticides, and on curing infected individuals, are only somewhat effective. The presence of animal reservoirs further complicates disease control and necessitates more effective controls, such as a vaccine.

The development of effective anti-trypanosomal vaccines has been unsuccessful because the parasite constantly displays different surface coat antigens (a process called antigenic variation) within its mammalian host. Researchers in the lab of Professor Serap Aksoy, Ph.D., are working to develop novel strategies to prevent trypanosome-induced disease by learning more about parasite development in tsetse, with the intention of inhibiting transmission from the fly to mammalian hosts.

More specifically, Aksoy’s team is developing a transmission-blocking vaccine that would prevent trypanosomes present in tsetse saliva from establishing an infection in the mammalian host bite site. Tsetse’s salivary glands harbor several developmental forms of the parasite, only one of which, the metacyclic, is able to establish an infection in mammals after the bite of an infectious fly. Aksoy and colleagues performed single-cell RNA sequencing of trypanosomes present in tsetse’s salivary glands and identified metacyclic cell genetic signatures that encode proteins unique to the surface of metacyclic cells.

In particular, the team discovered a new family of genes known as Fam10, one of which exhibited promising results when used as a vaccine antigen in laboratory tests. The onset of disease was significantly reduced in immunized mice compared with controls that received a non-metacyclic parasite vaccine antigen. Additional studies with Fam10 antigens are under way in Aksoy’s lab to enhance the efficacy of vaccines that block trypanosomal transmission.

“I think an effective vaccine against this disease is possible one day. This would be huge victory for public health and for Africa,” said Aksoy. “We are working diligently with our partners here and in Africa to help make this happen sooner.”