Our proposal addresses Human and Animal African Trypanosomosis (HAT and AAT, respectively), which are neglected diseases in Sub-Saharan Africa. The latest human epidemic with HAT caused hundreds of thousands of deaths since 1970s, and AAT remains rampant, causing severe economic burden in the continent. Sustainable disease elimination efforts are hampered because vaccines that can block parasite development in humans and animals are missing due to antigenic variation of the surface coat, which the parasites exhibit in the vertebrate host to escape antibody-mediated immune responses. We propose a novel vaccine strategy that will reduce transmission of HAT caused by Trypanosoma brucei rhodesiense (Tbr), and AAT caused by T. b. brucei (Tbb) and T. congolense (Tc) in animals. We will direct our vaccine efforts to the stage of trypanosomes introduced into the mammalian host by an infected tsetse fly bite (termed metacyclic). This could be a more effective attack against the parasite, since the parasite may be more vulnerable during the early stage of establishment in the host. Our approach is enabled by recent discoveries in the Tschudi laboratory that led to the first successful development of metacyclic Trypanosoma brucei spp. cultures in vitro, thus bypassing the need to obtain these from tsetse salivary glands. We will test the efficacy of cultured metacyclics as whole-organism vaccines. We have also identified two metacyclic-specific proteins that will serve as subunit vaccine targets. If successful, our discoveries will provide proof-of-principle for a modified Transmission Blocking Vaccine approach in the mammalian host that will protect dairy cattle, swine, and small ruminants from AAT. Our vaccines will also eliminate the animal reservoirs of human infective Tbr and reduce HAT transmission in East Africa. Finally, if successful in animals, the application of these vaccines in human hosts has the potential to eliminate HAT in Sub-Saharan Africa.
Submitted by Denise Meyer on May 18, 2016