title: Combination of CpG-oligodeoxynucleotides with recombinant ROP2 or GRA4 proteins induces protective immunity against Toxoplasma gondii infection.
abstract: Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) have been characterized as Th1-promoting immunopotentiators, an adjuvant activity desirable for vaccination against intracellular parasites like Toxoplasma gondii. In an attempt to find new antigen-adjuvant combinations that enhance the immunogenicity of antigen candidates for toxoplasma vaccines, we analyzed the extent of protection in mice immunized with ROP2 and GRA4 recombinant proteins when co-administered with CpG-ODN. Both GRA4+CpG-ODN and ROP2+CpG-ODN formulations were shown to induce a strong humoral Th1-biased response characterized by a high IgG(2a) to IgG(1) antibody ratio. Both vaccination regimens led to increased secretion of IFN-γ and IL-10, and negligible amounts of IL-4, upon specific re-stimulation of spleen cells from these groups of mice. After a non-lethal challenge with tissue cysts of a moderately virulent strain, only the brains from mice vaccinated with ROP2 or GRA4 in combination with CpG-ODN showed a significant reduction (63% and 62%, respectively) in their parasite load compared to the controls. The rate of protection obtained with GRA4+ROP2+CpG-ODN resulted equivalent (66%) to those achieved with the single antigens plus CpG-ODN. Taken together, these results indicate that CpG-ODN is an important candidate adjuvant for use in potential multicomponent anti-T. gondii vaccines for animals and humans.
authors.affiliation: Laboratorio de Inmunología, Centro de Salud y Medio Ambiente, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, Av. Gral. Paz 5445, San Martín, 1650 Buenos Aires, Argentina.
authors.forename: Vanesa R
authors.initials: VR
authors.lastname: Sánchez
authors.forename: Martín N
authors.initials: MN
authors.lastname: Pitkowski
authors.forename: Anahí V
authors.initials: AV
authors.lastname: Fernández Cuppari
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Rodríguez
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Fenoy
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Frank
authors.forename: Alejandra
authors.initials: A
authors.lastname: Goldman
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Corral
authors.forename: Valentina
authors.initials: V
authors.lastname: Martin
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D001921:Brain / Q000469:parasitology; D016207:Cytokines / Q000032:analysis; D005260:Female; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; C408982:CPG-oligonucleotide; D016207:Cytokines; C079248:GRA4 protein, Toxoplasma gondii; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C090555:ROP 2 protein, Toxoplasma gondii; D011994:Recombinant Proteins