Liver fluke vaccines in ruminants: strategies, progress and future opportunities.

The development of a vaccine for Fasciola spp. in livestock is a challenge and would be advanced by harnessing our knowledge of acquired immune mechanisms expressed by resistant livestock against fluke infection. Antibody-dependent cell-mediated cytotoxicity directed to the surface tegument of juvenile/immature flukes is a host immune effector mechanism, suggesting that antigens on the surface of young flukes may represent prime candidates for a fluke vaccine. A Type 1 immune response shortly after fluke infection is associated with resistance to infection in resistant sheep, indicating that vaccine formulations should attempt to induce Type 1 responses to enhance vaccine efficacy. In cattle or sheep, an optimal fluke vaccine would need to reduce mean fluke burdens in a herd below the threshold of 30-54 flukes to ensure sustainable production benefits. Fluke infection intensity data suggest that vaccine efficacy of approximately 80% is required to reduce fluke burdens below this threshold in most countries. With the increased global prevalence of triclabendazole-resistant Fasciolahepatica, it may be commercially feasible in the short term to introduce a fluke vaccine of reasonable efficacy that will provide economic benefits for producers in regions where chemical control of new drug-resistant fluke infections is not viable. Commercial partnerships will be needed to fast-track new candidate vaccines using acceptable adjuvants in relevant production animals, obviating the need to evaluate vaccine antigens in rodent models.

Galectin secretion and binding to adult Fasciola hepatica during chronic liver fluke infection of sheep.

Galectins are increasingly recognised as important mediators of immune homeostasis and disease regulation, but comparatively little is known about their role in parasite infection. This study investigates the interaction between two ovine galectins, galectin-11 and galectin-14, and the parasitic liver fluke, F. hepatica. Galectin-14 was found in eosinophils infiltrating the tissue surrounding infected bile ducts and secreted in the connective tissue, while galectin-11 was specifically induced in epithelial cells of bile ducts from infected sheep. Strong nuclear staining was observed for galectin-11. Both galectins were found to be secreted into the bile fluid of parasite infected sheep, and were also detected in the excretory/secretory products of adult flukes, following their removal from the ovine host. Recombinant galectin-14, but not recombinant galectin-11, was found to bind specifically to the surface tegument of adult flukes in a carbohydrate dependent manner. This study shows for the first time that both galectin-14 and galectin-11 are produced in liver tissue after chronic liver fluke infection and that they can directly interact with the parasite in the bile ducts. Galectin-11 may also be involved in epithelial cell turnover and cancerogenesis.

The relationship between the rapid rejection of Haemonchus contortus larvae with cells and mediators in abomasal tissues in immune sheep.

Rapid rejection or immune exclusion of challenge larvae is a well recognised phenomenon in sheep hypersensitised by repeated infection with gastrointestinal nematodes. While mast cells and globule leukocytes (GLs) are typically associated with this rapid rejection response, the exact mechanisms and mediators involved are not known. This study has adapted a recently developed ex vivo tissue explant model to examine in more detail the cells and mediators involved in preventing establishment of Haemonchus contortus L3s in abomasal tissue of sensitised sheep. Hypersensitisation of sheep by repeated larval infection resulted in a significant inhibition of larval establishment in abomasal tissue cultures and the extent of inhibition was dependent on the sensitisation dose. Both mast cells and GLs, but not eosinophils, were increased in abomasal tissues of hypersensitised sheep. Globule leucocyte numbers decreased significantly after 3h of culture, independent of the addition of L3s. In contrast, mast cell numbers only decreased after addition of L3s to the tissue cultures and this was associated with an increased release of histamine in tissue washes after incubation with L3s. Although, there was no significant difference in the number of tissue eosinophils between the groups, there was a marked increase in the eosinophil-specific protein, galectin-14, in tissue washes of the hypersensitised sheep after culture, suggesting eosinophils and their products may play a hitherto unrecognised role in the rapid rejection response. Further studies using specific inhibitors in this ex vivo tissue explant model may delineate the relative role of each cell population and mediator in the rapid rejection process.