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?

• Studying the transcriptomic response of ruminants to the acute and chronic stages of infection
• Identifying gene expression pathways involved in immunoregulation and whether these are open to manipulation
• Identify how animals that are considered more resistant are controlling/containing the infection. What are the roles of the various antibody classes and cellular responses.

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

The role of parasite glycans in the immune response, in immunomodulation and in the early stages of host-parasite
infection

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

• Study the response of “Resistant” animals compared to those that are highly susceptible
• Role of Molecular pattern recognition (interaction with TLRs) in determining the immune response.
• Cell types involved in the various stages of infection, including Th1/Th2
• balance in “resistant” and highly susceptible animals
• Identification of specific protective epitopes within putative vaccine antigens

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

A better understanding of the host-parasite interaction.

Existing knowledge including successes and failures

• In cattle a Th1 response with high titres of IgG2 and low titres of IgG1 has been correlated with protection.
• Conversely, infected animals produce specific IgG1 and almost no specific IgG2, and are not protected
• A proportion of the antibody response generated in natural infection may be directed at non-protective, “decoy” antigens