title: Bovine immune response to inoculation with Neospora caninum surface antigen SRS2 lipopeptides mimics immune response to infection with live parasites.
abstract: Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4(+) T-lymphocyte activation and gamma interferon (IFN-gamma) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4(+) cell proliferation and IFN-gamma T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-gamma secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-gamma-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-gamma secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Bustad Hall, Washington State University, Pullman, WA 99164-7040, USA. baszlert@vetmed.wsu.edu
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Baszler
authors.forename: Varda
authors.initials: V
authors.lastname: Shkap
authors.forename: Waithaka
authors.initials: W
authors.lastname: Mwangi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Davies
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Mathison
authors.forename: Monica
authors.initials: M
authors.lastname: Mazuz
authors.forename: Dror
authors.initials: D
authors.lastname: Resnikov
authors.forename: Lea
authors.initials: L
authors.lastname: Fish
authors.forename: Benjamin
authors.initials: B
authors.lastname: Leibovitch
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Staska
authors.forename: Igor
authors.initials: I
authors.lastname: Savitsky
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D002522:Chlorocebus aethiops; D003048:Coccidiosis / Q000276:immunology / Q000469:parasitology / Q000628:therapy / Q000662:veterinary*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008297:Male; D018688:Neospora / Q000276:immunology* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D008074:Lipoproteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C115389:SRS2 protein, Neospora caninum; D019444:Vaccines, DNA; D007371:Interferon-gamma