Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

Roberts, B., Antonopoulos, A., Haslam, S.M., Dicker, A.J., Mcneilly, T.N., Johnston, S.L., Dell, A., Knox, D.P. and Britton, C. (2013) Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans. Veterinary Research, 44, 111. (doi: 10.1186/1297-9716-44-111) (PMID:24289031) (PMCID:PMC4176091)

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Abstract

With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection. This is thought to be due to differences in glycosylation and/or conformation between native and recombinant proteins. We have exploited the free-living nematode Caenorhabditis elegans to examine its suitability as an alternative system for recombinant expression of parasitic nematode vaccine candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein, which is enriched in a gut membrane fraction capable of inducing significant protection against this important ovine gastrointestinal nematode. We show that H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass spectrometry identifies similar di- and tri-fucosylated structures to those on native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some glycan structural differences were observed, such as lack of LDNF. Serum antibody to native H11 binds to C. elegans recombinant H11 and most of the antibody to rH11 or native H11 is directed to glycan moieties. Despite these similarities, no reduction in worm burden or faecal egg count was observed following immunisation of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to the protective effect of H11 and that additional components present in native H11-enriched extract are likely required for enhancing the antibody response necessary for protection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mcneilly, Dr Tom and Britton, Dr Collette and Knox, Dr David
Authors: Roberts, B., Antonopoulos, A., Haslam, S.M., Dicker, A.J., Mcneilly, T.N., Johnston, S.L., Dell, A., Knox, D.P., and Britton, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Veterinary Research
Publisher:BioMed Central
ISSN:0928-4249
ISSN (Online):1297-9716
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Veterinary Research 44:111
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
453851Caenorhabditis elegans as an expression system for vaccine candidates of parasitic nematodesCollette BrittonBiotechnology and Biological Sciences Research Council (BBSRC)BB/F002033/1III - PARASITOLOGY