title: Immunisation with ID83 fusion protein induces antigen-specific cell mediated and humoral immune responses in cattle.
abstract: In this study we have investigated the potential of mycobacterial proteins as candidate subunit vaccines for bovine tuberculosis. In addition, we have explored the use of TLR-ligands as potential adjuvants in cattle. In vitro screening assays with whole blood from Mycobacterium bovis-infected and BCG-vaccinated cattle demonstrated that fusion protein constructs were most commonly recognised, and the ID83 fusion protein was selected for further immunisation studies. Furthermore, glucopyranosyl lipid A (GLA) and resiquimod (R848), agonists for TLR4 and TLR7/8 respectively, stimulated cytokine production (IL-12, TNF-α, MIP-1β and IL-10) in bovine dendritic cell cultures, and these were formulated as novel oil-in-water emulsions (GLA-SE and R848-SE) for immunisation studies. Immunisation with ID83 in a water-in-oil emulsion adjuvant (ISA70) induced both cell mediated and humoral immune responses, as characterised by antigen-specific IFN-γ production, cell proliferation, IgG1 and IgG2 antibody production. In comparison, ID83 immunisation with the novel adjuvants induced weaker (ID83/R848-SE) or no (ID83/GLA-SE) antigen-specific IFN-γ production and cell proliferation. However, both did induce ID83-specific antibody production, which was restricted to IgG1 antibody isotype. Overall, these results provide encouraging preliminary data for the further development of ID83 in vaccine strategies for bovine TB.
authors.affiliation: Department of Bovine TB, Animal Health and Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. Electronic address: gareth.j.jones@ahvla.gsi.gov.uk.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Jones
authors.forename: Sabine
authors.initials: S
authors.lastname: Steinbach
authors.forename: Derek
authors.initials: D
authors.lastname: Clifford
authors.forename: Susan L
authors.initials: SL
authors.lastname: Baldwin
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ireton
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D049109:Cell Proliferation; D007093:Imidazoles / Q000008:administration & dosage; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D009163:Mycobacterium bovis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000517:prevention & control*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007093:Imidazoles; D007074:Immunoglobulin G; D008050:Lipid A; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; C402365:resiquimod
keywords: Adjuvants; Bovine tuberculosis; Mycobacterium bovis; Vaccine