Low allelic diversity in vaccine candidates genes from different locations sustain hope for Fasciola hepatica immunization

Abstract Fasciola hepatica is a trematode parasite that causes fasciolosis in animals and humans. Fasciolosis is usually treated with triclabendazole, although drug-resistant parasites have been described in several geographical locations. An alternative to drug treatment would be the use of a vaccine, although vaccination studies that have been performed mainly in ruminants over the last 30 years, show high variability in the achieved protection and are not yet ready for commercialisation. Since F. hepatica exhibits a high degree of genomic polymorphism, variation in vaccine efficacy could be attributed, at least partially, to phenotypic differences in vaccine candidate sequences amongst parasites used in the challenge infections. To begin to address this issue, a collection of F. hepatica isolates from geographically dispersed regions, as well as parasites obtained from vaccination trials performed against a field isolate from Uruguay and the experimentally maintained South Gloucester isolate (Ridgeway Research, UK), were compiled to establish a F. hepatica Biobank. These collected isolates were used for the genetic analysis of several vaccine candidates that are important in host-parasite interactions and are the focus of the H2020 PARAGONE vaccine project ( https://www.paragoneh2020.eu/ ), namely FhCL1, FhCL2, FhPrx, FhLAP and FhHDM. Our results show that F. hepatica exhibits a high level of conservation in the sequences encoding each of these proteins. The consequential low variability in these vaccine candidates amongst parasites from different geographical regions reinforces the idea that they would be suitable immunogens against liver fluke isolates worldwide.