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?

• To identify antigens against which protective immune responses can be generated
• The parasite must be doing something which allows it to feed and evade the host responses as it migrates through the tissues – can these be used as immunogens
• Alternatively there may be factors which could be targeted such as gut antigens

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

Generation of genetically modified parasites lacking “virulence” factors or immunomodulators or use of RNAi technology

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

• Reverse vaccinology to identify possible protective antigens.
• Establish the identity and role of putative “virulence” factors and immunomodulators by generating genetically modified parasites.
• Establish which parasite genes are being expressed at different stages of feeding and their role
• PARAGONE, and EU-funded H2020 project involving vaccine development for liver fluke as well as for a range of other livestock parasites, will finish in 2019
• A Science-Foundation Ireland project on basic immunology and applied vaccine science will finish in 2020

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

Improved understanding of the mechanisms of protection
(i) The role of antibody classes in protection
(ii) The role of cell-mediated immune responses
(iii) Understanding the immuno-regulatory aspects of the target parasite
Transcriptomic studies of the host response

Existing knowledge including successes and failures

• Native fatty acid binding proteins induced 55% protection and cathepsin L1 42-69% protection in cattle.
• Native leucine aminopeptidase(LAP) induced 89% protection in sheep.
• Native glutathione S transferase – showed variable results in cattle and sheep
• Recombinant Schistosoma mansoni 14 antigen has shown positive results in some experiments.
• F.hepatica rLAP shown positive response in sheep
• Recombinant versions of Cl1 and CL3 have demonstrated protection in cattle