Genomic analysis of antigenic diversity in Brazilian Trypanosoma vivax strains

Project summary

Animal African trypanosomiasis (AAT) is a livestock disease caused by a blood parasite called Trypanosoma vivax. In South America, biting flies transmit T. vivax resulting in frequent AAT epidemics, substantial animal mortality and economic loss.

The development of vaccines against AAT in Brazil and elsewhere is a priority. A vaccine has enormous commercial potential in Brazil, which is the world’s largest beef exporter and where meat exports are around 7% of GDP. AAT infection reduces profit per animal by 11%, so a sustainable solution to AAT will have direct economic benefits to livestock production in Brazil and across South America. However, research on human trypanosomes has shown that they change their surface proteins to prevent the immune system from identifying and destroying them. Due to this process of antigenic variation, vaccination against AAT has generally been considered impossible.

However, our research on T. vivax has identified a suite of T. vivax-specific cell surface proteins that do not display antigenic variation, but do elicit strong immune responses in natural infections, and we have developed a system for producing T. vivax proteins for vaccination. One critical aspect of deciding if these antigens could work in a vaccine is their population genetics. To work universally, the vaccine antigen must be recognised every time a T. vivax infection occurs. This will only happen if the antigens are relatively well conserved across the parasites circulating in Brazil, which may have originated from multiple sources in Africa.

Our aim was to analyse genomic variation among Brazilian T. vivax genome sequences, to quantify the amount of variation in both Variant Surface Glycoprotein (VSG) genes and other, non-variant antigen genes. After comparing genomic repertoires of these gene families across Brazilian and African T. vivax strains, we concluded that these are largely conserved and not subject to frequent gene gain and loss, which would cause strains to diverge substantially over time. Our analysis of gene expression suggested that there could be substantial variation in which genes in the various families are expressed at a given time, which might compromise their use in a universal vaccine.

This project has provided key information on the natural polymorphism of Brazilian T. vivax antigens, which will be important when identifying a combination of protective antigens that can be used as an experimental vaccine in a clinical trial; this is an essential step in removing the burden of AAT on animal health and economic prosperity.