Exciting new research from University College Dublin partners paves way for fluke vaccine development

University College Dublin in conjunction with Queens University and Zoetis Inc., have recently published the article ‘Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica-infected and/or vaccinated cattle and identification of protective linear B-cell epitopes’. This study reflects one of the aims of PARAGONE-HORIZON 2020; the collaboration of academic institutions, in our case, University College Dublin and Queen’s University, with commercial organisations, such as Zoetis Inc., to achieve the common target of developing vaccines for control of parasitic diseases in farm animals.

The article focusses on the quest for an effective vaccine against the liver fluke, Fasciola hepatica. This complex parasite causes important economic losses in livestock and food industries around the world and it is also a significant zoonotic agent. Our group has been working for many years with a recombinant form of an immunodominant antigen as a vaccine candidate, the cysteine protease cathepsin L1(rmFhCL1) from F. hepatica. Vaccination of cattle with this antigen has provided protection against infection in some experimental trials, but not in others. We suggested that this inconsistency could be due to differential epitope recognition elicited by animals. Therefore, we have compared such epitope recognition in two independent trials, one showing partial vaccine protection and carried out by Zoetis (Kalamazoo, USA) and the other one, not showing vaccine efficacy and carried out in UCD. The animals in both trials were vaccinated with the same formula, rmFhCL1 plus a protease obtained from the juvenile stage (rFhCL3). Results showed for first time, that vaccinated animals having fluke burden reduction recognised regions 120-137, 145-155, 161-171 (CGSCWAFST, YMKNERTSISF, VDCSRPWGNNG) of FhCL1, which were not recognised by non-protected animals. In addition, the epitope WHQWKRM (aa 21-27), that is contained in the pro-peptide of FhCL1 (and FhCL3), was highly immunogenic following F. hepatica infection in both trials and both groups (vaccinated and controls) within each trial. Finally, we found that animals in the trial with partial protection had higher levels of IgG2 at the late infection. Hence, we have found that those two regions of the CL1 protein, together with the induction of specific IgG2, could be useful targets for improving vaccine strategies. Those protein sequences were localised in the 3D structure of FhCL1 which can be downloaded (free until March 24th 2018) from:
https://www.sciencedirect.com/science/article/pii/S0264410X18300549
https://doi.org/10.1016/j.vaccine.2018.01.020