title: Fusion of foreign T-cell epitopes and addition of TLR agonists enhance immunity against Neospora caninum profilin in cattle.
abstract: We demonstrated recently that immunization with recombinant Neospora caninum profilin (rNcPRO) induces limited protection and a regulatory T-cell response in mice. The aim of this study was to evaluate the immune response elicited by rNcPRO in cattle and assess a strategy to enhance its immunogenicity, combining the addition of T-cell epitopes and immune modulators. We developed a chimeric recombinant profilin fused to functional T-cell epitopes present in the N-terminal sequence of vesicular stomatitis virus (VSV) glycoprotein G (rNcPRO/G). Groups of three cattle were immunized with two doses (2 weeks apart) of rNcPRO or rNcPRO/G formulated with alum hydroxide or a nanoparticulated soya-based adjuvant enriched with Toll-like receptor (TLR) 2 and TLR9 agonists, aimed to tackle the MyD88 pathway (AVECplus). rNcPRO induced only a primary immune response (IgM mediated), while antibodies in rNcPRO/G-vaccinated animals switched to IgG1 after the booster. The vaccine formulated with rNcPRO/G and AVECplus improved the production of systemic IFN-γ and induced long-term recall B-cell responses. Overall, our study provides data supporting the use of T-cell epitopes from VSV glycoprotein G and TLR agonists to enhance and modulate immunity to peptide antigens in bovines, particularly when using small proteins from parasites for which immune responses are usually feeble.
authors: INTA-Instituto de Virología. Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Buenos Aires, Argentina.
authors: F C
authors: FC
authors: Mansilla
authors: INTA-Instituto de Virología. Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Buenos Aires, Argentina.|CONICET. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors: M E
authors: ME
authors: Quintana
authors: INTA-Instituto de Virología. Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Buenos Aires, Argentina.|CONICET. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors: N P
authors: NP
authors: Cardoso
authors: INTA-Instituto de Virología. Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Buenos Aires, Argentina. capozzo.alejandra@inta.gob.ar.|CONICET. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. capozzo.alejandra@inta.gob.ar.
authors: A V
authors: AV
authors: Capozzo
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology*; D003048:Coccidiosis / Q000276:immunology / Q000662:veterinary*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007074:Immunoglobulin G; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D018688:Neospora / Q000502:physiology*; D051304:Profilins / Q000032:analysis / Q000235:genetics; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D051304:Profilins; D016052:Protozoan Vaccines; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D007371:Interferon-gamma
keywords:  Neospora caninum ; cattle; profilin; recombinant vaccines