From genomes to vaccines via the proteome

Wilson, R. A.; Curwen, Rachel S.; Braschi, Bryony; Hall, Stephanie L.; Coulson, Patricia S.; Ashton, Peter D.

doi:10.1590/s0074-02762004000900008

Cited by 47 publications

(20 citation statements)

References 20 publications

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“…The burgeoning area of schistosome genomics and postgenomic research has been reviewed extensively (62,66,102,103,123,162,164), but one important point that needs to be made is that the majority of studies have been undertaken on S. mansoni and S. japonicum; there is almost a complete absence of transcriptome/genome information for S. haematobium, and this is clearly an important area for future study.…”

Section: New Antigen Discovery For Vaccines Against Schistosomesmentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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SUMMARY Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality. Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite. Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations. In particular, mass treatment does not prevent reinfection. Furthermore, there is increasing concern about the development of parasite resistance to PZQ. Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy. An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible. This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against the African (Schistosoma mansoni and S. haematobium) and Asian (S. japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack.

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Section: New Antigen Discovery For Vaccines Against Schistosomesmentioning

confidence: 99%

Current Status of Vaccines for Schistosomiasis

2008

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“…Among the currently available techniques, the combination of proteomics with serology (immunoproteomics (30 -34)) is largely being used to screen for panels of biomarkers and therapeutic targets in patients with infectious diseases (including SC (27,31,35,36)), cancer, or autoimmune disorders (32,(37)(38)(39)(40)(41). This discipline permits characterization of the immunome of a (micro)organism, defined as the subset of the proteome of a (micro)organism that acts as a target for the immune system (42). Remarkably its application in SC research has made it possible to cut back further the falsenegative rate associated with low antibody sensitivity in immunocompromised patients undergoing SC (36).…”

Section: Not Only Does Systemic Candidiasis (Sc)mentioning

confidence: 99%

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

Pitarch

Jiménez

Nombela

et al. 2006

Molecular & Cellular Proteomics

132

123

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In an effort to bring novel diagnostic and prognostic biomarkers or even potential targets for vaccine design for systemic candidiasis (SC) into the open, a systematic proteomic approach coupled with bioinformatic analysis was used to decode the serological response to Candida wall immunome in SC patients. Serum levels of IgG antibodies against Candida wall-associated proteins (proteins secreted from protoplasts in active wall regeneration, separated by two-dimensional gel electrophoresis, and identified by mass spectrometry) were measured in 45 SC patients, 57 non-SC patients, and 61 healthy subjects by Western blotting. Two-way hierarchical clustering and principal component analysis of their serum anti-Candida wall antibody expression patterns discriminated SC patients from controls and highlighted the heterogeneity of their expression profiles. Multivariate logistic regression models demonstrated that high levels of antibodies against glucan 1,3-␤-glucosidase (Bgl2p) and the antiwall phosphoglycerate kinase antibody seropositivity were the only independent predictors of SC. Receiver operating characteristic curve analysis revealed no difference between their combined evaluation and measurement of anti-Bgl2p antibodies alone. In a logistic regression model adjusted for known prognostic factors for mortality, SC patients with high anti-Bgl2p antibody levels or a positive anti-wall enolase antibody status, which correlated with each other, had a reduced 2-month risk of death. After controlling for each other, only the seropositivity for anti-wall enolase antibodies was an independent predictor of a lower risk of fatality, supporting that these mediated the protective effect. No association between serum anti-cytoplasmic enolase antibody levels and outcomes was established, suggesting a specific mechanism of enolase processing during wall biogenesis. We conclude that serum anti-Bgl2p antibodies are a novel accurate diagnostic biomarker for SC and that, at high levels,

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“…De una manera más específica podemos hablar de la immunoproteómica para describir el estudio de grandes conjuntos de proteínas implicados en la respuesta inmune (inmunoma) 23 , siendo sus principales aplicaciones: 1) el aislamiento e identificación mediante MS de proteínas pertenecientes al complejo principal de histocompatibilidad (MHC); 2) purificación e identificación de proteínas antigénicas de unión a anticuerpos específicos u otros reactivos de afinidad, y 3) identificación de las proteínas y las vías moduladas por un microorganismo específico, enfermedad infecciosa o toxina. Dentro del análisis del conjunto de proteínas incluidas en el MHC, una de las aplicaciones más interesantes de la inmunoproteómica consiste en el estudio de la respuesta serológica frente a un agente infeccioso y de las bases moleculares de su patogenicidad.…”

Section: Inmunoproteómicaunclassified