BBVac: Exploring genetic diversity and vaccine potential of TSR proteins against bovine babesiosis caused by three Babesia species

Bovine Babesiosis (BB) is a disease of cattle caused by a tick-transmitted single-celled parasite which enters, replicates, and then destroys red blood cells (RBCs). The disease is often fatal in cattle if no underlying immunity exists. 

BB affects cattle in tropical, subtropical but also temperature regions of the world. Whereas Babesia bovis and Babesia bigemina are BB-causing parasites of the tropics and subtropics, and widely distributed in Africa, Asia, Australia as well as Central and South America. Babesia divergens dominates in temperate climate regions such as Europe and is also a zoonotic agent. BB is on the rise with the tick vectors increasing their range, especially in Africa. Given the economic impact of the disease from large cattle ranges to subsistence farmers, better prevention methods need to be developed. Currently live attenuated vaccines are produced in some countries by government-sponsored programs. Although effective these have some disadvantages such as short shelf life, potential risk transmitting other cattle diseases as well as potential to reversion to virulence and regionally restricted efficacy. One way to overcome these disadvantages is the production of a subunit vaccine combining multiple antigens. The aim is to develop a commercially viable vaccine which prevents BB worldwide. 

To move closer towards this goal the genetic diversity of BB-causing parasites in the field needs determining. We propose to sequence 30 genomes from field isolates of B.bovis, B.bigemina and B.divergens from different regions in Argentina and UK. Using a more targeted approach we will study one gene family encoding TSR-proteins believed to be important for parasite motility by determining genetic diversity of individual TSR-domain proteins from additional field samples. Finally, we will explore the essentiality or redundancy of individual TSR-domain proteins for parasite growth by generating knockout parasites and test whether antibodies targeting these proteins can prevent the parasite from invasion in vitro.