Understanding the impact of parasitic co-infections on animal immune health in UK sheep

Summary:
Helminth parasites negatively impact animal health and welfare as the causative agents of over 55% of farm animal disease, resulting in economic costs estimated at £270 million per year in the UK. In sheep, the key drivers of parasitic disease are gastrointestinal nematodes (Teladorsagia circumcincta, Haemonchus contortus and Nematodirus battus) and the trematode Fasciola hepatica (liver fluke).
Following increasing reports of anthelmintic resistance, vaccines are viewed as an alternative method of helminth control. Developing vaccines for multicellular organisms such as helminths is challenging, and while positive results can be achieved by current prototype vaccines, efficacy has typically only been assessed in animals experimentally infected with the target parasite, with limited reproducibility.
Helminth vaccine design strategies are further hampered by the polarised T-helper type 2 (Th2) immune response that is driven by parasite molecules during infection; however, this is mainly extrapolated from murine studies. The complexities of host-parasite interactions in livestock and their impact on local and systemic immune responses, particularly during concurrent helminth infections and how they influence vaccine immunogenicity are still largely unknown.
This project addresses the complex nature of helminth infections in sheep on pasture in the UK and aims to define key immune signatures of infection that can be used for assessment of helminth vaccine efficacy on farm. Analysis of the immune response during concurrent parasitic infections will be carried out, which goes beyond previous studies that have focussed on gastrointestinal nematode infections, to address the impact of parasitic co-infections on overall animal immune health.
Sheep farm recruitment will use established farm networks developed by current BBSRC projects, and the CASE partner, Techion. Prevalence of parasites infecting sheep during a typical grazing/production season will be evaluated using diagnostic techniques to determine possible infections by gastrointestinal nematodes, liver fluke, Calicophoron daubneyi (rumen fluke) and coccidian protozoan parasites, including faecal egg/occyst counts and detection of parasite-specific antibodies by commercial and in-house ELISAs and IFATs.
The dynamics of parasitic co-infections will be investigated by means of: (a) parasite species diversity and abundance within individual animals; (b) potential impact of co-infection on parasite abundance/burden; (c) the impact on host immune responses to be evaluated using in vitro immunological assays including whole blood and immune cell stimulations, cytokine capture ELISAs, T lymphocyte population analysis, and RNASeq analysis. The data collected and generated from this project is critical for the translation and commercialisation of our experimental helminth vaccines to the farm setting.