Roadmap for the development of candidate vaccines for liver fluke

What are we trying to achieve and why? What is the problem we are trying to solve?

How the host-parasite interact allowing or otherwise parasite migration, feeding and reproduction

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

How is the very early stage of infection, across the intestinal mucosa, orchestrated

What approaches could/should be taken to address the research question?

• Establish which parasite genes are being expressed at different stages of feeding and their role in parasite feeding.
• Establish the degree of genetic variation there is in the parasite populations and the impact of these variations on the host-parasite interaction.
• Role of epithelial activation in initiating the immune responses.
• Establish the importance of the different interaction of tegumental Ags and ES Ags with TLR4 and dendritic cells.
• Establish the role of a range of Th2 cytokines, especially IL-25, IL-33 and TSLP
• Identify the parasite proteins/Ags that modulate dendritic cell maturation
• Establish the role of basophils early in infection
• Establish the role of Antibody-dependent Cell cytotoxicity

What else needs to be done before we can solve this need?

Parasite genome sequence – annotated

Existing knowledge including successes and failures

• In Schistosoma infected mice after an early phase of antigen specific cellular proliferation and IFNγ synthesis there is a shift to a Th2 profile with LI-4 and IL-13 production predominating and a decrease in cellular responses. By the time infection becomes patent the response is dominated by IL-10 and TGFβ and IgG1 predominates.
• Initial recognition of the metacercariae takes place in the GIT.
• The tegument of NEJs is primarily composed on oligomannose and core fucosylated truncated N-glycans .Ttegumatal Ag induce angeric T-cells via dendritic cells
• In both cattle and sheep IgG2 are linked with the expression of resistance or protection