Abstract
Roundworm parasite infections are a major cause of human and livestock disease worldwide and a threat to global food security. Disease control currently relies on anthelmintic drugs to which roundworms are becoming increasingly resistant. An alternative approach is control by vaccination and ‘hidden antigens’, components of the worm gut not encountered by the infected host, have been exploited to produce Barbervax, the first commercial vaccine for a gut dwelling nematode of any host. Here we present the structure of H-gal-GP, a hidden antigen from Haemonchus contortus, the Barber’s Pole worm, and a major component of Barbervax. We demonstrate its novel architecture, subunit composition and topology, flexibility and heterogeneity using cryo-electron microscopy, mass spectrometry, and modelling. Importantly, we demonstrate that complexes with the same architecture are present in other Strongylid roundworm parasites including human hookworm. This suggests a common ancestry and the potential for development of a unified hidden antigen vaccine.
Highlights
Roundworm parasites, gastrointestinal species, are the most important cause of livestock disease affecting the world’s poor, causing greatly reduced production efficiency [1, 2] and as such are a threat to global food security
Roundworm parasites are responsible for disease within both animal and human populations with Ancylostomiasis affecting over 500 million a year and the Trichostrongylids causing significant animal health and production harm to global livestock industries
We reveal the structure of H-gal-GP by cryo-electron microscopy and use negative-stain EM to show that T. circumcincta, O. ostertagi and A. ceylanicum all have complexes with a similar overall architecture
Summary
Gastrointestinal species, are the most important cause of livestock disease affecting the world’s poor, causing greatly reduced production efficiency [1, 2] and as such are a threat to global food security. They are important causes of veterinary disease in high income countries, costing the Australian sheep industry >$430 million per annum [3, 4]. To date only two vaccines are available commercially for any roundworm parasites of any host (Bovilis Huskvac and Barbervax, for sheep and goats) and a vaccine based on hookworm gut-expressed antigens is in Phase I clinical trials [10]
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