title: Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response.
abstract: The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Hernández
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Van Coppernolle
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Borloo
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Van Meulder
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Oonagh
authors.initials: O
authors.lastname: Paerewijck
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Iris
authors.initials: I
authors.lastname: Peelaers
authors.affiliation: Laboratory of Experimental Immunology, Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: Claerebout
authors.affiliation: Laboratory of Parasitology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Sciences, Ghent University, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Geldhof
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000469:parasitology* / Q000517:prevention & control; D005767:Gastrointestinal Diseases / Q000469:parasitology / Q000517:prevention & control* / Q000662:veterinary; D015801:Helminth Proteins / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010028:Ostertagia / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D062605:Quillaja Saponins / Q000008:administration & dosage / Q000276:immunology; D014611:Vaccination / Q000662:veterinary*
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D062605:Quillaja Saponins; D000536:Aluminum Hydroxide; C046386:Quil A; D007371:Interferon-gamma