Use of immunopeptidomics to inform development of the next generation of tropical theileriosis vaccines

Project summary

Tropical theileriosis is a major disease that constrains the productivity and genetic improvement of cattle and buffalo across North Africa, the Middle East and Asia. The disease is caused by the tick-transmitted parasite Theileria annulata and leads to severe animal illness, with annual economic losses of $7 billion. Currently, prevention of this economically important disease is limited to the use of: (1) tick treatments, which are toxic, expensive and becoming ineffective due to drug resistance and/or (2) live Th. annulata-infected cell line vaccines, which have a number of practical constraints, specifically the requirement for a liquid nitrogen cold chain and variable effectiveness. Hence, better understanding of protective immune responses in Th. annulata infection is required with an urgent need to develop improved vaccines.

Studies indicate that immunity to Th. annulata is cell mediated, with roles for CD8+ T-cells in killing infected host cells, and CD4+ T-cells in promoting and sustaining a functionally mature CD8+ T-cell population. Thus, development of novel subunit vaccines will be dependent on the identification of parasite peptides that can be recognised by CD4+ T-cells as well as CD8+ T-cells. Due to the large size of the Th. annulata proteome and diversity of the bovine MHC (the molecules that present peptides for recognition by T-cells), antigen identification persists as a major obstacle to rationalised vaccine development.

Advances in mass spectrometry offer new opportunities to characterise pathogen peptides that are presented to CD8+ and CD4+ T-cells by the host MHC molecules (MHCI and MHCII, respectively) and so capable of eliciting pathogen-specific T-cell responses. The approach, termed immunopeptidomics, has recently been applied in cattle to study Th. parva peptides presented by MHCI and MHCII-DR molecules to CD8+ T-cells and CD4+ T-cells, respectively, but has not be applied to studying bovine MHCII-DQ presented peptides. This study proposes to apply immunopeptidomics to characterise the Th. annulata-peptides presented by MHCII-DQ. The study will provide detailed information that can be utilised in a variety of ways to accelerate the identification of novel candidate antigens and so the development of the next generation of Th. annulata vaccines.