Following the 2016 ECF Consortium annual meeting in May 2016, participants in the project drafted short blog posts about different aspects of their work related to East Coast fever (ECF) vaccine development. This post was contributed by Nicola Ternette (University of Oxord) and Tim Connelley (University of Edinburgh).
For some diseases, the development of vaccines has been proven to be challenging due to the fact that there is limited knowledge of which parts of the pathogen are actually visible to the immune system during infection.
We are here aiming to directly identify the parts or ‘antigens’ of the Theileria parva parasite that are visible to the cellular immune system during infection using a state-of-the-art mass spectrometry approach in order to inform the development of targeted vaccines against Theileriosis.
Particularly for parasitic diseases the development of vaccines has not been successful to date. East Coast fever (or Theileriosis) in cattle and is the most important life stock disease affecting sub-Saharan Africa with an estimated loss of around 1 Million animals per year . It has been identified by the Bill and Melinda Gates Foundation as one of the key livestock diseases in Sub-Saharan Africa. It is caused by Theileria parva, a parasite that is related to the Plasmodium parasite that causes Malaria in humans.
We are aiming to directly identify the parts of the parasite that are visible to the cellular immune system during infection to inform vaccine development. These parts, or ‘antigens’, are small peptide molecules that are short strings of parasite proteins. These peptides are bound to larger proteins, so called bovine leukocyte antigens (BoLA), on the surface of the infected cell. The BoLA-bound peptides can be recognized by white blood cells as foreign antigens. A subpopulation of these cells, called cytotoxic T lymphocytes, are able to eliminate the infected cell upon recognition of the antigen.
Knowledge of the nature of these parasite antigens that are presented during infection will provide direct information for vaccine design as we need to train the immune system to target such sequences presented during infection.
At the Jenner Institute in Oxford and Roslin Institute in Edinburgh, we have developed a method to purify BoLA-bound peptides from infected cells and use mass spectrometry to identify their amino acid sequences. This information enables us to conclude, which protein the T cell antigens originate from and which proteins to include in the vaccines.
However, the nature of the BoLA antigens are not identical in individual cattle and in addition also vary between breeds. Therefore, we are aiming to further develop this platform in order to achieve high throughput screening of individual animals and different breeds. The obtained datasets will then enable us to identify common Theileria parva antigens that are presented on the surface of infected cells between animals and breeds.
Such antigens are exciting new vaccine candidates as they will allow us to elicit targeted immune responses in animals that will be relevant for protection of cattle against East Coast Fever.