Due to high mortality and morbidity rates livestock diseases are an impediment to the livelihoods of poor farmers in Africa, who struggle to attain food and nutritional and economic security. Vaccines can alleviate such constraints as they are among the most successful disease interventions invented. The goal of this project is to increase cattle productivity through the development of improved vaccines for the control of East Coast fever (ECF).
East Coast fever caused by the protozoan parasite Theileria parva ranks first in tick-borne disease constraints of cattle in sub-Saharan Africa and kills one animal every 30 seconds. It has a devastating impact on pastoralists and smallholder farmers because it can kill within 3-4 weeks of infection. East Coast fever is present in 11 countries where roughly 28 million cattle are at risk, but has the potential to spread with the uncontrolled movement of infected cattle as the distribution of the tick vector and suitable tick habitats is wider than that of the parasite. Over one million cattle die of East Coast fever each year resulting in annual losses exceeding $300 million. The project goal is to design subunit vaccines for the control of East Coast fever. In phase 1, the project will undertake a range of key strategic activities in the research to product development continuum to:
- Improve aspects of the current sub-optimal live (infection and treatment method - ITM) East Coast fever vaccine.
- Fill knowledge gaps regarding the qualitative and quantitative aspects of acquired immune responses that mediate immunity to East Coast fever.
- Test the vaccine potential of candidate vaccine antigens and develop a more detailed antigen map.
Outputs from this phase will contribute in the short-term to production of a better quality live vaccine as an interim vaccine solution and provide proof-of-concept for an East Coast fever subunit vaccine aimed at obtaining evidence of protection in 70~80% of animals of defined histocompatibility complex (MHC) genotype given a homologous parasite challenge. Success in phase 1 will contribute to our goal of developing a broad-spectrum subunit vaccine for the control of East Coast fever (phase 2).
The project objectives are:
1. To improve aspects of the current live infection and treatment method East Coast fever vaccine. This is a short-term objective over two years that should give rise to methods for determining viable sporozoite counts and relating this to infectivity, which will enable downstream improvements to be made to the production of the infection-and-treatment method (ITM) vaccine; e.g., stabilate titration, pre-determining smaller dose sizes and testing new cryo-protectants.
Key milestone: a new method for viable sporozoite counts.
2. To induce antibody based immunity by targeting the sporozoite stage of the parasite. This is a medium-term objective over 2~4 years, which should result in re-assessment of the role of known as well as novel sporozoite molecules as candidate vaccine antigens.
Key milestones: a denser map of sporozoite antigens and evidence for a role for antigens in a subunit vaccine.
3. To induce T-cell mediated immunity by targeting the schizont stage of the parasite. This is a medium-term objective over 4 years, which will improve our knowledge on how the process of ITM works, assess a variety of antigen delivery systems for priming cytotoxic T lymphocytes (CTLs) in cattle and identify new schizont T cell antigens.
Key milestones: role of other cells in priming CD8+ T cells, molecular signatures of protection, a denser map of schizont antigens, proof-of-concept of a schizont vaccine.
4. Application of evolutionary and comparative pathogen genomics to East Coast fever vaccinology. This is a medium-term objective over 3 years, which will improve genomic resources for T. parva.
Key milestones: improved genome annotation, antigen identification and a map of genetic variation.
5. To test if a combined antibody and T-cell mediated immune response is more efficacious than either one alone. This is a medium- term objective in the second half of the project, which will test if targeting immune responses to both the sporozoite and schizont stage of the parasite works synergistically. These experiments will be especially useful if testing of sporozoite and schizont antigens in isolation does not provide high levels of immunity.
Key milestone: proof-of-concept vaccine targeting two parasite stages.