%0 Journal Article
%T Structure of the protective nematode protease complex H-gal-GP and its conservation across roundworm parasites
%A Alexander. H. Jamson
%A Charlotte A. Scarff
%A Christopher Kennaway
%A Chun-Feng Song
%A Elida M. Rabelo
%A George F. J. Newlands
%A John Trinick
%A Rebecca F. Thompson
%A Stephen P. Muench
%A Vivian J. da Silva
%A W. David Smith
%J -
%D 2020
%R 10.1371/journal.ppat.1008465
%X 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
%K Proteases
%K Parasitic diseases
%K Vaccines
%K Electron cryo-microscopy
%K Hemoglobin
%K Veterinary parasitology
%K Blood
%K Nematode infections
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008465