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      Toxoplasma gondii Protein Disulfide Isomerase (TgPDI) Is a Novel Vaccine Candidate against Toxoplasmosis

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          Abstract

          Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 μg of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 μg rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-γ), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis.

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          Most cited references 48

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          Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease.

           Laura Howe,  L. Sibley (1995)
          The population genetic structure of Toxoplasma gondii was determined by multilocus restriction fragment length polymorphism analysis at 6 loci in 106 independent isolates from humans and animals. Phylogenetic and statistical analyses indicated a highly unusual population structure consisting of 3 widespread clonal lineages. Extensively mixed genotypes were only apparent in 4 strains, which indicated that, while not separate species, sexual recombination between the 3 lineages is exceedingly rare in natural populations. T. gondii is a major cause of subclinical human infection and an important opportunistic pathogen that causes severe disease in immunocompromised patients. While strains from all 3 lineages were isolated from humans, the majority of human toxoplasmosis cases were associated with strains of a type II genotype. The correlation of specific clonal lineages with human toxoplasmosis has important implications for development of vaccines, drug treatments, and diagnostic protocols.
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            Protein disulfide isomerase.

            During the maturation of extracellular proteins, disulfide bonds that chemically cross-link specific cysteines are often added to stabilize a protein or to join it covalently to other proteins. Disulfide formation, which requires a change in the covalent structure of the protein, occurs as the protein folds into its three-dimensional structure. In the eukaryotic endoplasmic reticulum and in the bacterial periplasm, an elaborate system of chaperones and folding catalysts ensure that disulfides connect the proper cysteines and that the folding protein does not make improper interactions. This review focuses specifically on one of these folding assistants, protein disulfide isomerase (PDI), an enzyme that catalyzes disulfide formation and isomerization and a chaperone that inhibits aggregation.
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              Foodborne toxoplasmosis.

              Toxoplasmosis can be due to congenital infection or acquired infection after birth and is one of the leading illnesses associated with foodborne hospitalizations and deaths. Undercooked meat, especially pork, lamb, and wild game meat, and soil contaminated with cat feces on raw fruits and vegetables are the major sources of foodborne transmission for humans. The new trend in the production of free-range organically raised meat could increase the risk of Toxoplasma gondii contamination of meat. Foodborne transmission can be prevented by production practices that reduce T. gondii in meat, adequate cooking of meat, washing of raw fruits and vegetables, prevention of cross contamination in the kitchen, and measures that decrease spread of viable oocysts into the environment.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                15 August 2013
                : 8
                : 8
                Affiliations
                [1 ]Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China
                [2 ]Department of Physiology, Key Laboratory of Cellular Physiology Co-constructed by Province and Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, PR China
                [3 ]Center of Laboratory Animal, Shanxi Medical University, Taiyuan, Shanxi, PR China
                Charité, Campus Benjamin Franklin, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: G-RY. Performed the experiments: H-LW Y-QL MG. Analyzed the data: L-TY X-LM. Contributed reagents/materials/analysis tools: H-LL J-JL. Wrote the paper: H-LW J-HZ.

                Article
                PONE-D-13-05767
                10.1371/journal.pone.0070884
                3744524
                23967128

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 9
                Funding
                This work was supported by the National Natural Science Foundation of China (No. 81071374) and the 331 Early Career Researcher Grant of Shanxi Medical University (No. 201202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Immunochemistry
                Immunology
                Immunity
                Immunity to Infections
                Immune Response
                Microbiology
                Parasitology
                Quantitative Parasitology
                Medicine
                Infectious Diseases
                Parasitic Diseases
                Toxoplasmosis
                Public Health
                Immunizations

                Uncategorized

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