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      Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

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          Abstract

          Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione- S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

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          Most cited references77

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            Whole-genome sequence of Schistosoma haematobium.

            Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
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              Schistosoma mansoni: chemotherapy of infections of different ages.

              Mice were treated with potassium antimony tartrate, hycanthone, oxamniquine, niridazole, or praziquantel at different times after infection with Schistosoma mansoni. The rate of cure was assessed by perfusion of surviving worms approximately 4 weeks after treatment, and the percentage reduction in worm burden was estimated relative to the number of adult worms perfused from control mice, comparably infected but untreated. All six drugs were relatively inactive against S. mansoni between 3 and 4 weeks after infection when compared with treatment at 5 to 6 weeks. However, the drugs differed in the patterns of cure they achieved in the 2-week period after administration of cercariae and in the period around the onset of patency. Worms that had been subjected to amoscanate or hycanthone in the third week after infection showed evidence of this as adults in having a reduced fecundity. Factors such as worm or host physiology, or host immune status may have had roles in the outcome of chemotherapy at different stages of maturation of S. mansoni.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                05 May 2015
                2015
                : 6
                : 213
                Affiliations
                [1] 1Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University , Cairns, QLD, Australia
                [2] 2QIMR Berghofer Medical Research Institute , Brisbane, QLD, Australia
                [3] 3University of Melbourne , Melbourne, VIC, Australia
                [4] 4Centro de Pesquisas Rene Rachou, Oswaldo Cruz Foundation , Belo Horizonte, Brazil
                [5] 5Federal University of Minas Gerais , Belo Horizonte, Brazil
                [6] 6National Institute of Parasitic Diseases , Shanghai, China
                [7] 7National Institutes of Health Research , Harare, Zimbabwe
                [8] 8Department of Biochemistry, University of Zimbabwe , Harare, Zimbabwe
                [9] 9Department of Biology, University of York , York, UK
                [10] 10Department of Microbiology, Immunology and Tropical Medicine, George Washington University , Washington, DC, USA
                [11] 11University of Edinburgh , Edinburgh, UK
                [12] 12University of California Irvine , Irvine, CA, USA
                Author notes

                Edited by: Rashika El Ridi, Cairo University, Egypt

                Reviewed by: Mauricio Martins Rodrigues, Federal University of São Paulo, Brazil; Rasha Soliman, Suez Canal University, Egypt; Taif University, Egypt

                *Correspondence: Alex Loukas, Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Building E4, McGregor Road, Cairns, QLD 4878, Australia, alex.loukas@ 123456jcu.edu.au

                Specialty section: This article was submitted to Immunotherapies and Vaccines, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2015.00213
                4419842
                25999951
                61d95f86-5ce7-4195-9870-cfc5024bb2e3
                Copyright © 2015 Pearson, Becker, Driguez, Young, Gaze, Mendes, Li, Doolan, Midzi, Mduluza, McManus, Wilson, Bethony, Nausch, Mutapi, Felgner and Loukas.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 March 2015
                : 18 April 2015
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 96, Pages: 13, Words: 10413
                Funding
                Funded by: National Institutes of Health in Harare and the Biochemistry Department at University of Zimbabwe
                Funded by: National Health and Medical Research Council of Australia (NHMRC)
                Award ID: APP1037304
                Funded by: Wellcome Trust UK
                Award ID: WT082028MA
                Funded by: Cunningham Trust
                Funded by: Carnegie Trust for the Universities of Scotland
                Funded by: Shanghai Science and Technology Commission
                Award ID: 15ZR1444300
                Categories
                Immunology
                Original Research

                Immunology
                schistosomiasis,protein microarray,vaccine,human,drug-induced resistance
                Immunology
                schistosomiasis, protein microarray, vaccine, human, drug-induced resistance

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