title: Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites.
abstract: Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an attractive and efficient model for vaccine development in toxoplasmosis.
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédica, USP, Av. Prof. Lineu Prestes, 1374, Edifício Biomédicas II Cidade Universitária, São Paulo, SP, CEP: 05508-000, Brazil.|Laboratório de Protozoologia, Instituto de Medicina Tropical de São Paulo, FMUSP, USP, Av. Dr. Enéas de Carvalho Aguiar, 470, 1° Andar, São Paulo, SP, CEP: 05403-000, Brazil.
authors.forename: Nahiara Esteves
authors.initials: NE
authors.lastname: Zorgi
authors.affiliation: Laboratório de Protozoologia, Instituto de Medicina Tropical de São Paulo, FMUSP, USP, Av. Dr. Enéas de Carvalho Aguiar, 470, 1° Andar, São Paulo, SP, CEP: 05403-000, Brazil.
authors.forename: Andrés Jimenez
authors.initials: AJ
authors.lastname: Galisteo
authors.affiliation: Departamento de Dermatologia, Instituto de Medicina Tropical de São Paulo, FMUSP, USP, Av. Dr. Enéas de Carvalho Aguiar, 470, 3° Andar, São Paulo, SP, CEP: 05403-000, Brazil.
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Pesquisas Energéticas e Nucleares, IPEN, Rua Travessa 400, Cidade Universitária, São Paulo, SP, CEP: 05508-900, Brazil.
authors.forename: Nanci
authors.initials: N
authors.lastname: do Nascimento
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédica, USP, Av. Prof. Lineu Prestes, 1374, Edifício Biomédicas II Cidade Universitária, São Paulo, SP, CEP: 05508-000, Brazil. hfandrad@usp.br.|Laboratório de Protozoologia, Instituto de Medicina Tropical de São Paulo, FMUSP, USP, Av. Dr. Enéas de Carvalho Aguiar, 470, 1° Andar, São Paulo, SP, CEP: 05403-000, Brazil. hfandrad@usp.br.|Department of Pathology, Faculty of Medicine, Universidade de São Paulo, São Paulo, Brazil. hfandrad@usp.br.
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D001769:Blood / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007274:Injections, Intraperitoneal; D008297:Male; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016052:Protozoan Vaccines; D015164:Vaccines, Inactivated
keywords: B lymphocytes; CD4+ T lymphocytes; CD8+ T lymphocytes; Ionizing radiation; Toxoplasma gondii; Vaccine