Molecular and serological characteristics of the glutathione S‐transferases of <i>Schistosoma japonicum</i> and <i>Schistosoma mansoni</i>

Tiu, Wilfred U.; Davern, Kathy M.; Wright, Mark D.; Board, P.G.; Mitchell, Graham F.

doi:10.1111/j.1365-3024.1988.tb00255.x

Cited by 50 publications

(12 citation statements)

References 28 publications

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“…Mice vaccinated with DNA that contained the SmCT-SOD gene seemed to react with GST (Fig. 4D), although previous reports showed that there was no cross-reactivity between the S. japonicum (Sj26) GST and the S. mansoni counterpart in mice (28,64). However, as this reactivity occurred only at a very low titer (1:80), we considered such reactivity irrelevant in our study.…”

Section: Discussionmentioning

confidence: 84%

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Carvalho-Queiroz¹,

Cook²,

Wang

et al. 2004

Infect Immun

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Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.Schistosomiasis remains an endemic problem in over 76 countries, although approaches to reduce transmission and morbidity as well as to improve sanitation, mollusciciding and mass chemotherapy, have been attempted (3, 13). Vaccine development to control schistosomiasis is a high priority, as it would offer the potential of cost-efficient, long-lasting prophylaxis (2, 65). Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. Larval parasite killing mechanisms include the release of oxidants by eosinophils, neutrophils, and macrophages potentiated by antibodies and/or cytokines (8,12,16,31,32). However, to establish itself in the host, the parasite has evolved a number of immune evasion mechanisms (17,39,51,60), such as antioxidant enzymes (7,11,30,37). These are essential enzymes involved in the prevention of reactive oxygen species-derived damage. Evidence for the involvement of schistosome antioxidant enzymes, such as cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), in immune evasion has been presented elsewhere (39). SmCT-SOD and GPX localize to the host-parasite interface (worm tegument and gut epithelium of the adult but not the larval schistosome) (41) and show developmental regulation (29,41,42) wit...

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Section: Discussionmentioning

confidence: 84%

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Carvalho-Queiroz¹,

Cook²,

Wang

et al. 2004

Infect Immun

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“…Mention should be made that neither Iodogen nor Chloramine T methods were able to label these proteins. The reason remains unknown but this observation could be related to the work of Tiu et al (1988) who reported similar results concerning the Schistosoma japonicum 26 kDa G S T . This might be due not to an absence of tyrosine in the molecules but rather to the non-accessibility of such residues during labelling.…”

Section: Immunogenicity Of Tcgbp During Human and Experimental Chagasmentioning

confidence: 75%

Trypanosoma cruziglutathione-binding proteins: immunogenicity during human and experimental Chagas' disease

et al. 1992

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Following purification by affinity chromatography, three glutathione-binding proteins (TcGBP) of 45, 30, and 25 kDa were co-purified from Trypanosoma cruzi epimastigotes. Using 1-chloro-2,4 dinitrobenzene as substrate, a glutathione S-transferase activity of 70 nmol/min/mg of proteins was detected in the GSH binding fraction. An increased expression of TcGBP and total GST activity was observed upon incubation of parasites with phenobarbital, which is an inducer of GST synthesis. Immunofluorescence and electron microscopic experiments demonstrated that TcGBP were expressed by all developmental stages of the parasite, including infective forms. The expression of these proteins by intracellular dividing amastigotes could be in favour of a potential defensive role of these molecules against host attack. Results obtained by immunoprecipitation of in vitro translation products using anti-TcGBP antisera suggested that these three polypeptides are not glycosylated. In addition, antibodies directed against the TcGBP were found in a high proportion of T. cruzi-infected chronic chagasic patients' sera and in sera of chronically infected BALB/c mice. In contrast, acute chagasic patients' sera and acute-phase mouse sera were found to be poorly reactive with these proteins. Our results identify a new class of potential target antigens, which may be essential for the development of T. cruzi in its host. Their protective role in experimental models deserves to be investigated.

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“…A 26 KDa isoenzyme of S.japonicum glutathione S-transferase (Sj26GST), which catalyses detoxification of lipophilic molecules by thioconjugation, is one of the six antigens recommended by WHO for vaccine development [24]. It has been shown that the reduction of worm burdens and liver egg numbers in mice can reach 30.1% and 44.8%, respectively, after immunization with a plasmid containing Sj26GST DNA (pVAX1-Sj26GST) [25].…”

Section: Introductionmentioning

confidence: 99%

Partial Regulatory T Cell Depletion Prior to Schistosomiasis Vaccination Does Not Enhance the Protection

et al. 2012

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CD4+CD25+ regulatory T cells (Tregs) do not only influence self-antigen specific immune responses, but also dampen the protective effect induced by a number of vaccines. The impact of CD4+CD25+ Tregs on vaccines against schistosomiasis, a neglected tropical disease that is a major public health concern, however, has not been examined. In this study, a DNA vaccine encoding a 26 kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST) was constructed and its potential effects were evaluated by depleting CD25+ cells prior to pVAX1-Sj26GST immunization. This work shows that removal of CD25+ cells prior to immunization with the pVAX1-Sj26GST schistosomiasis DNA vaccine significantly increases the proliferation of splenocytes and IgG levels. However, CD25+ cell-depleted mice immunized with pVAX1-Sj26GST show no improved protection against S. japonicum. Furthermore, depletion of CD25+ cells causes an increase in both pro-inflammatory cytokines (e.g. IFN-γ, GM-CSF and IL-4) and an anti-inflammatory cytokine (e.g. IL-10), with CD4+CD25- T cells being one of the major sources of both IFN-γ and IL-10. These findings indicate that partial CD25+ cell depletion fails to enhance the effectiveness of the schistosome vaccine, possibly due to IL-10 production by CD4+CD25- T cells, or other cell types, after CD25+ cell depletion during vaccination.

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Molecular and serological characteristics of the glutathione S‐transferases of Schistosoma japonicum and Schistosoma mansoni

Cited by 50 publications

References 28 publications

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Trypanosoma cruziglutathione-binding proteins: immunogenicity during human and experimental Chagas' disease

Partial Regulatory T Cell Depletion Prior to Schistosomiasis Vaccination Does Not Enhance the Protection

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