I). Functional and antigenic characterisation of Fasciola hepatica liver fluke glycoproteins to identify novel preventive intervention approaches (SNF-Ambizione)

The zoonotic liver fluke Fasciola hepatica is a parasite responsible for major economic losses to the agriculture industry worldwide. Correspondingly, the prevalence of Fasciola hepatica infections in dairy cattle in Switzerland is over 16%. Triclabendazole (TCBZ) has been the drug of choice for the treatment of fasciolosis. However, financial losses are mainly attributed to subclinical infections, and resistance to TCBZ is becoming more prevalent with cases of resistance detected across different countries. There is a significant focus on the development of new approaches for the prevention and control of fasciolosis in livestock based on novel protein vaccine candidates. In this process however, parasitic glycoproteins – being abundant constituents of the liver flukes and the major targeted antigens in infections – have to date been mostly ignored. Protein glycosylation is one of the most common and highly heterogeneous posttranslational modification. More than 50% of eukaryotic proteins are predicted to be glycosylated and can influence a variety of cellular and pathobiological processes. For example, F. hepatica glycoproteins exhibit immunomodulatory properties. By inducing a specific humoral host response, essential fluke glycoproteins serve as a source of candidate vaccine antigens. In this project, initially the F. hepatica life-stage site-specific glycoproteome will be characterized by a quantitative “glycomics” approach. A combinatorial pipeline based on the comprehensive glycoproteomic data set and a detailed functional- and antigenic characterization of parasite stage-specific glycoproteins aims to uncover vaccine candidates, which will be further evaluated in proof-of-principle vaccine trials. The prospective results will reveal new ways by which liver flukes interact with the host and how this evolutionary adaptation might be harnessed in the development of desperately needed novel preventive intervention approaches.

 

Institute members: Ramon M. Eichenberger (Project Leader), Sina Hasler (Assistant)

External members: Prof. Markus Aebi & Dr Timothy G. Keys (Department of Biology, ETH Zurich, Switzerland), Prof. Alex Loukas (AITHM, James Cook University, Australia), Chia-Wei Lin (FGCZ, Switzerland)

Other links to external web pages: http://p3.snf.ch/project-185865

Funding sources: SNSF Ambizione (#185865)