title: Ovine IgA-reactive proteins from Teladorsagia circumcincta infective larvae.
abstract: Infection of small ruminants with Teladorsagia circumcincta has, until now, been controlled using a combination of pasture management and frequent anthelmintic treatments. Resistance to the commonly used anthelmintics has driven research into the development of a subunit vaccine, encouraged by the demonstration of development of protective immunity in sheep following exposure to this parasite. Local immune effectors in the abomasum, in particular IgA, are thought to play important roles in naturally- and experimentally-acquired immunity. L3s represent the first contact of this pathogen with the host immune system and, herein, the presence of L3 antigen-specific IgA was demonstrated in abomasal mucus from immune sheep. This antibody source was used to immunoaffinity purify and identify IgA-reactive molecules present in L3s. We identified 155 different proteins in this way, including a number of activation-associated secretory proteins, venom allergen-like-type proteins, detoxifying enzymes, galectins and a suite of other potential vaccine candidate molecules. Levels of immunoaffinity-enriched L3 antigen-specific IgA in gastric lymph from previously-infected sheep were statistically significantly higher (P=0.004) than those measured in helminth-free sheep and a statistically significant negative correlation (P=0.005, rs=-0.565) was identified between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and total T. circumcincta burden measured at necropsy. In addition, a statistically significant positive correlation (P=0.007, rs=0.534) was measured between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and the percentage of inhibited L4s enumerated at necropsy. These results indicate that the purified antigens contain components that could be strongly considered as vaccine candidates.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK; Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Ellis
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK.
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Matthews
authors.affiliation: Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin, Midlothian EH25 9RG, UK.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Shaw
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Paterson
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Victoria, Australia.
authors.forename: Hamish E G
authors.initials: HE
authors.lastname: McWilliam
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK.
authors.forename: Neil F
authors.initials: NF
authors.lastname: Inglis
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK. Electronic address: Alasdair.Nisbet@moredun.ac.uk.
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Nisbet
mesh_terms: D000018:Abomasum / Q000378:metabolism; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D007070:Immunoglobulin A / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008196:Lymph / Q000737:chemistry / Q000378:metabolism; D009093:Mucus / Q000737:chemistry / Q000378:metabolism; D009348:Nematoda / Q000378:metabolism*; D012756:Sheep; D059467:Transcriptome
chemical_list: D007070:Immunoglobulin A
keywords: Gastric lymph; IgA; Sheep; Teladorsagia circumcincta; Vaccine candidates