title: Successful immunization against a parasitic nematode by vaccination with recombinant proteins.
abstract: Infection of humans and livestock with parasitic nematodes can have devastating effects on health and production, affecting food security in both developed and developing regions. Despite decades of research, the development of recombinant sub-unit vaccines against these pathogens has been largely unsuccessful. We have developed a strategy to identify protective antigens from Teladorsagia circumcincta, the major pathogen causing parasitic gastroenteritis in small ruminants in temperate regions, by studying IgA responses directed at proteins specific to post-infective larvae. Antigens were also selected on the basis of their potential immunomodulatory role at the host/parasite interface. Recombinant versions of eight molecules identified by immunoproteomics, homology with vaccine candidates in other nematodes and/or with potential immunoregulatory activities, were therefore administered to sheep in a single vaccine formulation. The vaccine was administered three times with Quil A adjuvant and the animals subsequently subjected to a repeated challenge infection designed to mimic field conditions. Levels of protection in the vaccinates were compared to those obtained in sheep administered with Quil A alone. The trial was performed on two occasions. In both trials, vaccinates had significantly lower mean fecal worm egg counts (FWECs) over the sampling period, with a mean reduction in egg output of 70% (Trial 1) and 58% (Trial 2). During the period of peak worm egg shedding, vaccinates shed 92% and 73% fewer eggs than did controls in Trials 1 and 2, respectively. At post mortem, vaccinates had 75% (Trial 1) and 56% (Trial 2) lower adult nematode burdens than the controls. These levels of protection are the highest observed in any system using a nematode recombinant sub-unit vaccine in the definitive ruminant host and indicate that control of parasitic helminths via vaccination with recombinant subunit vaccine cocktails is indeed an alternative option in the face of multi-drug resistance.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Edinburgh EH26 0PZ, United Kingdom. Alasdair.Nisbet@moredun.ac.uk
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Nisbet
authors.forename: Tom N
authors.initials: TN
authors.lastname: McNeilly
authors.forename: Louise A
authors.initials: LA
authors.lastname: Wildblood
authors.forename: Alison A
authors.initials: AA
authors.lastname: Morrison
authors.forename: David J
authors.initials: DJ
authors.lastname: Bartley
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bartley
authors.forename: Cassandra
authors.initials: C
authors.lastname: Longhi
authors.forename: Iain J
authors.initials: IJ
authors.lastname: McKendrick
authors.forename: Javier
authors.initials: J
authors.lastname: Palarea-Albaladejo
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Matthews
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D005243:Feces / Q000469:parasitology; D012756:Sheep / Q000276:immunology; D012757:Sheep Diseases / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017183:Strongylida / Q000472:pathogenicity*; D017206:Strongylida Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D014614:Vaccines, Synthetic
keywords: Nematode; Sub-unit vaccine; Teladorsagia circumcincta