title: Vaccination-induced protection of lambs against the parasitic nematode Haemonchus contortus correlates with high IgG antibody responses to the LDNF glycan antigen.
abstract: Lambs respond to vaccination against bacteria and viruses but have a poor immunological response to nematodes. Here we report that they are protected against the parasitic nematode Haemonchus contortus after vaccination with excretory/secretory (ES) glycoproteins using Alhydrogel as an adjuvant. Lambs immunized with ES in Alhydrogel and challenged with 300 L3 larvae/kg body weight had a reduction in cumulative egg output of 89% and an increased percentage protection of 54% compared with the adjuvant control group. Compared to the adjuvant dimethyl dioctadecyl ammonium bromide, Alhydrogel induced earlier onset and significantly higher ES- specific IgG, IgA, and IgE antibody responses. In all vaccinated groups a substantial proportion of the antibody response was directed against glycan epitopes, irrespective of the adjuvant used. In lambs vaccinated with ES in Alhydrogel but not in any other group a significant increase was found in antibody levels against the GalNAcbeta1,4 (Fucalpha1,3)GlcNAc (fucosylated LacdiNAc, LDNF) antigen, a carbohydrate antigen that is also involved in the host defense against the human parasite Schistosoma mansoni. In lambs the LDNF-specific response increased from the first immunization onward and was significantly higher in protected lambs. In addition, an isotype switch from LDNF-specific IgM to IgG was induced that correlated with protection. These data demonstrate that hyporesponsiveness of lambs to H. contortus can be overcome by vaccination with ES glycoproteins in a strong T-helper 2 type response-inducing aluminum adjuvant. This combination generated high and specific antiglycan antibody responses that may contribute to the vaccination-induced protection.
authors.affiliation: Utrecht University, Department of Infectious Diseases and Immunology, Division of Parasitology and Tropical Veterinary Medicine, PO Box 80.165, 3508 TD Utrecht, The Netherlands. l.vervelde@vet.uu.nl
authors.forename: Lonneke
authors.initials: L
authors.lastname: Vervelde
authors.forename: Nicole
authors.initials: N
authors.lastname: Bakker
authors.forename: Frans N J
authors.initials: FN
authors.lastname: Kooyman
authors.forename: Albert W C A
authors.initials: AW
authors.lastname: Cornelissen
authors.forename: Christine M C
authors.initials: CM
authors.lastname: Bank
authors.forename: A Kwame
authors.initials: AK
authors.lastname: Nyame
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000947:Antigens, Helminth / Q000276:immunology* / Q000627:therapeutic use; D006188:Haemonchiasis / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D006189:Haemonchus / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007785:Lactose / Q000031:analogs & derivatives / Q000276:immunology* / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D014611:Vaccination / Q000662:veterinary*
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; C488538:N-acetylgalactosaminyl-1-4-(fucosyl-1,3)-N-acetylglucosamine; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D000536:Aluminum Hydroxide; D007785:Lactose