Genomic comparisons of trypanosomatid veterinary vaccine vehicles optimised for different target species

Supervisors: Professor Keith R Matthews, Dr Al Ivens

Project Description:

Many livestock species harbour non-pathogenic trypanosome parasites without effects on their well-being or productivity. Examples are cattle, which harbour Trypanosoma theileri, and sheep, which harbour Trypanosoma melophagium. These trypanosomatids show exquisite host and vector specificity, with T. theileri being spread between bovines by tabanid flies and T. melophagium being transmitted between ovines by sheep keds. Each of these species is being developed as a vaccine delivery vehicle, such that they are engineered to express vaccine antigens and- when inoculated as a live vaccine- stimulate the immune response of the recipient animals over an extended period. The ease of genetic manipulation and long-term survival of the trypanosomatids in their livestock host offers exciting potential for these organisms to be a novel, effective and flexible alternative to conventional prime boost vaccination. This has particular advantages in settings where veterinary management is challenging, such as in the developing world.

We have recently completed and published the genome sequence of Trypanosoma theileri, revealing a number of interesting differences to the better characterised pathogenic trypanosomes of humans (T. brucei, T. cruzi). For T. melophagium, the analysis of a few genes and intergenic regions indicates that they are extremely closely related to T. theileri. This raises the question of what governs their host and vector specificity. In this project, we will derive and analyse the genome sequence of T. melophagium in relation to the existing T. theileri sequence to identify determinants of their specificity for sheep and sheep keds. The function of identified differences can also be assayed using genetic manipulation tools that we have already developed for both T. theileri and T. melophagium. Analysis of their host and vector specificity will address the origins and evolution of their adaptations. This will be relevant for the development of these trypanosomatids as vaccine delivery vehicles, but will also inform on the evolutionary biology of host and vector specificity which could be relevant for pathogenic and zoonotic trypanosomatids.

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