Vaccine potential of recombinant cathepsin B against Fasciola gigantica

Chantree, Pathanin; Phatsara, Manussabhorn; Meemon, Krai; Chaichanasak, Pannigan; Changklungmoa, Narin; Kueakhai, Pornanan; Lorsuwannarat, Natcha; Sangpairoj, Kant; Songkoomkrong, Sineenart; Wanichanon, Chaitip; Itagaki, Tadashi; Sobhon, Prasert

doi:10.1016/j.exppara.2013.06.010

Cited by 32 publications

(23 citation statements)

References 34 publications

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“…One approach that can expedite drug discovery process is to find new uses for existing approved compounds, a practice commonly known as drug repositioning or repurposing [17] . Drug repositioning has proved to be an efficient way of identifying new therapies against neglected tropical diseases.…”

Section: Introductionmentioning

confidence: 99%

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

et al. 2015

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Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes.

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Section: Introductionmentioning

confidence: 99%

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

et al. 2015

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“…In contrast, in the FhSAP2-IBs vaccinated animals enhanced levels of both IgG1 and IgG2a antibodies were detected, implicating mixed Th1/Th2 antibody response associated to the protection. Although is not clear the role of antibodies in the protection against F. hepatica this type of mixed humoral response has been reported by other vaccination studies in both F. hepatica and F. gigantica (Chantree et al, 2013; Golden et al, 2010; Kueakhai et al, 2013; Preyavichyapugdee et al, 2008). Moreover, the observation that FhSAP2-IBs vaccinated animals developed significantly higher levels of IgG2a, companied with high levels of serum IFNγ and TNFα, and significantly lower levels of IL-4 than controls support the hypothesis that the Th1-response could be necessary to induce protection against fascioliasis, which has been also suggested by other authors (Hacariz et al, 2009).…”

Section: Discussionmentioning

confidence: 71%

“…Over the last decade a large number of native and recombinant parasite proteins have been identified and tested as vaccine in a number of animals models. Some of these molecules includes leucinaminopeptidase (Maggioli et al, 2011a), cathepsin-L (Chantree et al, 2013; Golden et al, 2010; Piacenza et al, 1999), thioredoxin-glutathion reductase (Maggioli et al, 2011b), glutathione S-transferase (Sexton et al, 1990; Sexton et al, 1994), fatty acid binding protein (Casanueva et al, 2001; Martinez-Fernandez et al, 2004) and saposin-like protein-2 (Espino et al, 2010; Kueakhai et al, 2013). All these vaccine candidates have induced partial levels of protection that range between 46.9–83% in different animal models, which indicates that a vaccine against F. hepatica is not a chimera but an attainable goal.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Rivera

Espino

2016

Experimental Parasitology

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Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund’s adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide™ ISA720. Animals received three injections containing 20μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0–62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells.

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“…Due to an unique “occluding loop,” these cysteine proteases can block the access of substrates and inhibitors in human (Musil et al, 1991 ; Illy et al, 1997 ). Recently, these cysteine proteases were found to play a key role in the biology of trematodes and to be important virulence factors in a picomplexan parasite Eimeria tenella (Rieux et al, 2012 ), liver fluke parasites Fasciola hepatica (Beckham et al, 2009 ) and Fasciola gigantica (Siricoon et al, 2012 ; Chantree et al, 2013 ). Previous study also shown that cowpea bruchids could fend off plant defensive efforts, such as dietary soybean cysteine protease inhibitor (scN), by over-expression of major digestive cathepsin L-like proteases as well as by activating scN-insensitive cathepsin B-like proteases (Moon et al, 2004 ; Koo et al, 2008 ; Jongsma and Beekwilder, 2011 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of host-associated differentiation in Bemisia tabaci (Hemiptera: Aleyrodidae)

Xie

Wang

et al. 2014

Front. Physiol.

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Host-associated differentiation is one of the driving forces behind the diversification of phytophagous insects. In this study, host induced transcriptomic differences were investigated in the sweetpotato whitefly Bemisia tabaci, an invasive agricultural pest worldwide. Comparative transcriptomic analyses using coding sequence (CDS), 5′ and 3′ untranslated regions (UTR) showed that sequence divergences between the original host plant, cabbage, and the derived hosts, including cotton, cucumber and tomato, were 0.11–0.14%, 0.19–0.26%, and 0.15–0.21%, respectively. In comparison to the derived hosts, 418 female and 303 male transcripts, respectively, were up-regulated in the original cabbage strain. Among them, 17 transcripts were consistently up-regulated in both female and male whiteflies originated from the cabbage host. Specifically, two ESTs annotated as Cathepsin B or Cathepsin B-like genes were significantly up-regulated in the original cabbage strain, representing a transcriptomic response to the dietary challenges imposed by the host shifting. Results from our transcriptome analysis, in conjunction with previous reports documenting the minor changes in their reproductive capacity, insecticide susceptibility, symbiotic composition and feeding behavior, suggest that the impact of host-associated differentiation in whiteflies is limited. Furthermore, it is unlikely the major factor contributing to their rapid range expansion/invasiveness.

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Vaccine potential of recombinant cathepsin B against Fasciola gigantica

Cited by 32 publications

References 34 publications

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Transcriptome analysis of host-associated differentiation in Bemisia tabaci (Hemiptera: Aleyrodidae)

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