Abstract

Fasciola hepatica is the causative agent of fasciolosis, a significant parasitic disease occurring worldwide. Despite ongoing efforts, there is still no vaccine to control liver fluke infections in livestock. Recently, it has been suggested that natural antibodies (NAbs) can amplify specific antibodies (SpAb) and have a direct killing effect, but it is unknown if this phenomenon occurs during parasitic helminth infection or targeted vaccination. NAbs are antibodies produced by the innate immune system, capable of binding antigens without prior exposure. This study explores the role of bovine NAbs, using the exogenous glycoprotein keyhole limpet hemocyanin (KLH), in response to F. hepatica infection and SpAb production after infection and vaccination. The cattle’s NAbs were differently influenced by parasite infection and vaccination, with an increase in KLH-binding IgG and IgM levels after infection and reduced KLH-binding IgM levels following vaccination. Underlying NAbs reacting to KLH showed no correlations to the final fluke burdens after experimental infection or vaccination. However, NAbs reacting to whole-worm extract (WWE) prior to infection were positively correlated to increased fluke burdens within the infected bovine host. Furthermore, after infection, the specific IgG reacting to WWE was positively reflected by the underlying NAb IgG response. Following subcutaneous vaccination with F. hepatica native glutathione S-transferase (GST), there was a non-significant 33% reduction in fluke burden. Vaccinated animals with higher underlying NAbs had a higher induction of vaccine-induced SpAbs, with trends observed between KLH-binding IgM and anti-GST IgG and IgM. Our findings provide a platform to allow further investigation to determine if NAb levels could mirror fluke-SpAb production for exploitation in a combined selective breeding and vaccination program. Additionally, this work suggests that liver fluke could possibly evade the host’s immune system by utilising surface-bound IgM NAbs.

Highlights

  • Introduction tional affiliationsThe livestock industry is a vital global commodity under increasing pressure due to the growing population and food demands [1]

  • To investigate if natural antibodies (NAbs) have an effect on parasite infections in cattle, the fluke burdens were determined from a group of cattle vaccinated with a combination of native F. hepatica

  • We investigated if bovine NAb levels can reflect the subsequent vaccine-induced specific antibody responses towards glutathione S-transferase following vaccination and if NAbs link to final fluke numbers after experimental infection

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Summary

Introduction

The livestock industry is a vital global commodity under increasing pressure due to the growing population and food demands [1]. The globally distributed Fasciola spp. cause upwards of US $3.2 billion per annum in lost revenue in livestock production and associated control measures [4,5]. Current control of liver fluke infections heavily relies on anthelmintics, triclabendazole, but drug resistance to triclabendazole has been reported on multiple continents [6,7]. These reports highlight the need to develop a sustainable and effective vaccine to diminish the production losses resulting from fasciolosis. The majority of vaccine studies against F. hepatica resulted in a lack of significant efficacy and the repeatability required for commercialisation

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