Authors

R Lalor³; A McEvoy²; J López Corrales³; S Ellis²; C De Marco Verissimo³; O Keane²; JP Dalton³; K Cwiklinski¹;  ¹ University of Liverpool, UK;  ² Teagasc, Ireland;  ³ University of Galway, Ireland

Discussion

The ongoing effort to develop a liver fluke vaccine has been greatly enhanced by the major advances in our knowledge of liver fluke biology, facilitated by the availability of large sequencing datasets and biochemical analyses. Based on this data, our vaccine candidate selection strategy has focussed on disrupting key biological processes by combining groups of antigens with similar/complementary functional actions into a single vaccine cocktail. In this study, we used size exclusion chromatography to fractionate adult worm excretory-secretory protein products to further interrogate the molecules secreted by Fasciola hepatica. The protein composition of each fraction was ascertained by proteomic analyses. The most abundant proteins present in each fraction were selected for recombinant protein expression. Two sheep vaccine trials were carried out over two consecutive years to evaluate the vaccine efficacy of four native fractions versus recombinant protein cocktails that recreated the native protein fraction composition, each formulated in the adjuvant Montanide 61 VG (Seppic). Distinct antibody and cell mediated responses were elicited in both trials by the native fraction vaccines, which were comparable to their recombinant counterparts. This implies that post-translational modifications of the proteins examined were not relevant in the protective immune responses elicited. While no significant reduction in liver fluke burden was observed for any of the vaccine cocktails, the animals vaccinated with the native fraction composed of glycolytic enzymes displayed a significantly greater weight gain relative to the other vaccine groups and the non-vaccinated control group. The impact on weight loss is consistent with previous sheep vaccine trials performed in our laboratory and highlights the positive impact vaccination can have on animal welfare without statistically reducing parasite burdens. These studies also highlight the need for studies to be repeated in different larger cohorts of animals to obtain significantly robust measures of vaccine efficacy and reproducibility.