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?

Generation of a protective immune response against F.hepatica using parasite peptides/glycopeptides giving protection for up to a year.

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

• Lack of a natural boosting effect from field exposure if hidden antigens are used
• Immunomodulation by field infection
• Obtaining protective immune responses in the range of MHC haplotypes represented in target populations, given the limited T-cell epitopes likely to be represented in a peptide-based vaccine
• Obtaining recombinants that mimic the protective capacity of native proteins in the case of a sub-unit vaccine

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

• Identify antigens that are physiologically important for the parasite’s development and or survival – secreted or hidden.
• Identify of secreted antigens that the parasite uses to modulate host responses
• Produce effective recombinants and/or peptides that induce protective, but not decoy or deleterious responses

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

• A challenge model
• Definition of minimal acceptable efficacy
• Identity of adjuvants to give long lasting protective immune responses.
• Identity of suitable expression vectors for large scale expression.
• Identity of protective antigens

Existing knowledge including successes and failures

• Vaccine trials are under way evaluating a range of antigens.
• Excretory products have been trialled – including cathepsin L2, GST, HDM, PRx, LAP