Abstract

Some nematode species are economically important parasites of livestock, while others are important human pathogens causing some of the most important neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost effective strategy. Currently, Barbervax® for the ruminant strongylid Haemonchus contortus is the only registered subunit vaccine for a nematode parasite, although a vaccine for the human hookworm Necator americanus is undergoing clinical trials (HOOKVAC consortium). As both these vaccines comprise a limited number of proteins, there is potential for selection of nematodes with altered sequences or expression of the vaccine antigens. Here we compared the transcriptome of H. contortus populations from sheep vaccinated with Barbervax® with worms from control animals. Barbervax® antigens are native integral membrane proteins isolated from the brush border of the intestinal cells of the adult parasite and many of those are proteases. Our findings provide no evidence for changes in expression of genes encoding Barbervax® antigens in the surviving parasite populations. However, surviving parasites from vaccinated animals showed increased expression of other proteases and regulators of lysosome trafficking, and displayed up-regulated lipid storage and defecation abilities that may have circumvented the effect of the vaccine. Implications for other potential vaccines for human and veterinary nematodes are discussed.

Highlights

  • Gastrointestinal nematodes (GINs) are clinically and economically important parasites of humans (Hotez et al, 2016) and livestock species (Kaplan and Vidyashankar, 2012), impeding both human health and wealth (Rist et al, 2015)

  • Parasitological data confirmed a significant reduction in H. contortus infection following Barbervax vaccination

  • In comparison with the development of drug resistance, vaccine resistance has rarely been reported in viruses or bacteria (Kennedy and Read, 2017)

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Summary

Introduction

Gastrointestinal nematodes (GINs) are clinically and economically important parasites of humans (Hotez et al, 2016) and livestock species (Kaplan and Vidyashankar, 2012), impeding both human health and wealth (Rist et al, 2015). Greater research efforts are being directed at vaccine development for more sustainable GIN control in both veterinary and human settings (Hewitson and Maizels, 2014; Hotez et al, 2016). In comparison with antimicrobial drugs, there are few examples of the development of resistance to vaccination in bacterial or viral pathogens (Kennedy and Read, 2017).

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