title: Immunization with Neospora caninum profilin induces limited protection and a regulatory T-cell response in mice.
abstract: Profilins are actin-binding proteins that regulate the polymerization of actin filaments. In apicomplexan parasites, they are essential for invasion. Profilins also trigger the immune response of the host by activating TLRs on dendritic cells (DCs), inducing the production of pro-inflammatory cytokines. In this study we characterized for the first time the immune response and protection elicited by a vaccine based on Neospora caninum profilin in mice. Groups of eight BALB/c mice received either two doses of a recombinant N. caninum profilin expressed in Escherichia coli. (rNcPRO) or PBS, both formulated with an aqueous soy-based adjuvant enriched in TLR-agonists. Specific anti-profilin antibodies were detected in rNcPRO-vaccinated animals, mainly IgM and IgG3, which were consumed after infection. Splenocytes from rNcPRO-immunized animals proliferated after an in vitro stimulation with rNcPRO before and after challenge. An impairment of the cellular response was observed in NcPRO vaccinated and infected mice following an in vitro stimulation with native antigens of N. caninum, related to an increase in the percentage of CD4+CD25+FoxP3+. Two out of five rNcPRO-vaccinated challenged mice were protected; they were negative for parasite DNA in the brain and showed no histopathological lesions, which were found in all PBS-vaccinated animals. As a whole, our results provide evidence of a regulatory response elicited by immunization with rNcPRO, and suggest a role of profilin in the modulation and/or evasion of immune responses against N. caninum.
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires, Argentina.
authors.forename: Florencia Celeste
authors.initials: FC
authors.lastname: Mansilla
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Quintana
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Langellotti
authors.affiliation: Tecnovax S.A, Luis Viale 2835, 1416 Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Wilda
authors.affiliation: Instituto de Ciencia y Tecnología Dr. César Milstein, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinez
authors.affiliation: Instituto de Ciencia y Tecnología Dr. César Milstein, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Adriana
authors.initials: A
authors.lastname: Fonzo
authors.affiliation: Estación Experimental Agropecuaria, INTA Balcarce, Buenos Aires, Argentina.
authors.forename: Dadín Prando
authors.initials: DP
authors.lastname: Moore
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires, Argentina.
authors.forename: Nancy
authors.initials: N
authors.lastname: Cardoso
authors.affiliation: Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Buenos Aires, Argentina. Electronic address: capozzo.alejandra@inta.gob.ar.
authors.forename: Alejandra Victoria
authors.initials: AV
authors.lastname: Capozzo
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D003048:Coccidiosis / Q000276:immunology / Q000517:prevention & control*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018688:Neospora / Q000276:immunology*; D051304:Profilins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000592:standards; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D016415:Sequence Alignment; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000592:standards
chemical_list: D000913:Antibodies, Protozoan; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D051304:Profilins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
keywords: Dendritic cells; Neospora caninum; Profilin; Regulatory response; Vaccine