title: Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice.
abstract: Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.
authors.affiliation: Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Camila Figueiredo
authors.initials: CF
authors.lastname: Pinzan
authors.affiliation: Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Sardinha-Silva
authors.affiliation: Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fausto
authors.initials: F
authors.lastname: Almeida
authors.affiliation: Division of Molecular Biosciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom.
authors.forename: Livia
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Carla Duque
authors.initials: CD
authors.lastname: Lopes
authors.affiliation: Department of Medicine, Division of Rheumatology, University of California Los Angeles, Los Angeles, California, 90095-1670, United States of America.
authors.forename: Elaine Vicente
authors.initials: EV
authors.lastname: Lourenço
authors.affiliation: Department of Biology, School of Philosophy, Sciences and Literature of Ribeirão Preto, University of Sao Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ademilson
authors.initials: A
authors.lastname: Panunto-Castelo
authors.affiliation: Division of Molecular Biosciences, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
authors.affiliation: Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Roque-Barreira
mesh_terms: D000818:Animals; D001921:Brain / Q000469:parasitology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000276:immunology*; D016052:Protozoan Vaccines / Q000096:biosynthesis / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D016207:Cytokines; D015800:Protozoan Proteins; D016052:Protozoan Vaccines