The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Patrick Driguez - One of the best experts on this subject based on the ideXlab platform.
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An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2016Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Tiago Mendes, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immun
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an Immunomics approach to schistosome antigen discovery antibody signatures of naturally resistant and chronically infected individuals from endemic areas
PLOS Pathogens, 2014Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Tiago Antonio De Oliveira Mendes, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2014Co-Authors: Faculty Publications Microbiology, Patrick Driguez, Denise L Doolan, Tropical Medicine, Mark S. Pearson, Tiago Mendes, Soraya GazeAbstract:An Immunomics approach to schistosome antigen discovery: Antibody signatures of naturally resistant and chronically infected individuals from endemic areas Soraya Gaz
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REVIEW Open Access
2013Co-Authors: Patrick Driguez, Denise L Doolan, Phillip L Felgner, Alex Loukas, Donald P McmanusAbstract:The recent publication of the Schistosoma japonicum and S. mansoni genomes has expanded greatly the opportunities for post-genomic schistosomiasis vaccine research. Immunomics protein microarrays provide an excellent application of this new schistosome sequence information, having been utilised successfully for vaccine antigen discovery with a range of bacterial and viral pathogens, and malaria. Accordingly, we have designed and manufactured a Schistosoma Immunomics protein microarray as a vaccine discovery tool. The microarray protein selection combined previously published data and in silico screening of available sequences for potential immunogens based on protein location, homology to known protective antigens, and high specificity to schistosome species. Following cloning, selected sequences were expressed cell-free and contact-printed onto nitrocellulose microarrays. The reactivity of microarray proteins with antisera from schistosomiasisexposed/resistant animals or human patients can be measured with labelled secondary antibodies and a laser microarray scanner; highly reactive proteins can be further assessed as putative vaccines. This highly innovative technology has the potential to transform vaccine research for schistosomiasis and other parasitic diseases of humans and animals. Revie
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Novel immunomic technologies for schistosome vaccine development
Parasite immunology, 2012Co-Authors: Hamish E G Mcwilliam, Patrick Driguez, Donald P Mcmanus, David Piedrafita, Els N.t. MeeusenAbstract:SUMMARY Schistosomiasis remains one of the most common human helminthiases, despite the availability of an effective drug against the causative parasites. Drug treatment programmes have several limitations, and it is likely that a vaccine is required for effective control. While decades of vaccine development have seen the discovery and testing of several candidate antigens, none have shown consistent and acceptable high levels of protection. The migrating larval stages are susceptible to immunity, however few larval-specific antigens have been discovered. Therefore, there is a need to identify novel larval-specific antigens, which may prove to be more efficacious than existing targets. Immunomics, a relatively new field developed to cope with the recent large influx of biological information, holds promise for the discovery of vaccine targets, and this review highlights some immunomic approaches to schistosome vaccine development. Firstly, a method to focus on the immune response elicited by the important and vulnerable larval stage is described, which allows a targeted study of the immunome at different tissue sites. Then, two high-throughput arrays are discussed for the identification of protein and carbohydrate antigens. It is anticipated that these approaches will progress vaccine development against the schistosomes, as well as other parasites.
Denise L Doolan - One of the best experts on this subject based on the ideXlab platform.
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Immunomics guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis a biomarker identification study
The Lancet Microbe, 2021Co-Authors: Mark S. Pearson, Denise L Doolan, Bemnet Amare Tedla, Luke Becker, Rie Nakajima, Gebeyaw G Mekonnen, Carla Proietti, Al Jasinskas, Abena S Amoah, Stefanie KnoppAbstract:Summary Background Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field. Methods We did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format. Findings From array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC]serum=0·98 [95% CI 0·95–1·00]; AUCurine=0·96 [0·93–0·99]), and MS3_01370 (AUCserum=0·93 [0·89–0·97]; AUCurine=0·81 [0·72–0·89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0·79 [0·69–0·90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%. Interpretation We identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance. Funding Australian Trade and Investment Commission and Merck Global Health Institute.
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An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2016Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Tiago Mendes, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immun
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Immunomics a 21st century approach to vaccine development for complex pathogens
Parasitology, 2016Co-Authors: Karina Pires De Sousa, Denise L DoolanAbstract:Immunomics is a relatively new field of research which integrates the disciplines of immunology, genomics, proteomics, transcriptomics and bioinformatics to characterize the host-pathogen interface. Herein, we discuss how rapid advances in molecular immunology, sophisticated tools and molecular databases are facilitating in-depth exploration of the immunome. In our opinion, an Immunomics-based approach presides over traditional antigen and vaccine discovery methods that have proved ineffective for highly complex pathogens such as the causative agents of malaria, tuberculosis and schistosomiasis that have evolved genetic and immunological host-parasite adaptations over time. By using an integrative multidisciplinary approach, Immunomics offers enormous potential to advance 21st century antigen discovery and rational vaccine design against complex pathogens such as the Plasmodium parasite.
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an Immunomics approach to schistosome antigen discovery antibody signatures of naturally resistant and chronically infected individuals from endemic areas
PLOS Pathogens, 2014Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Tiago Antonio De Oliveira Mendes, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2014Co-Authors: Faculty Publications Microbiology, Patrick Driguez, Denise L Doolan, Tropical Medicine, Mark S. Pearson, Tiago Mendes, Soraya GazeAbstract:An Immunomics approach to schistosome antigen discovery: Antibody signatures of naturally resistant and chronically infected individuals from endemic areas Soraya Gaz
Donald P Mcmanus - One of the best experts on this subject based on the ideXlab platform.
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An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2016Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Tiago Mendes, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immun
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an Immunomics approach to schistosome antigen discovery antibody signatures of naturally resistant and chronically infected individuals from endemic areas
PLOS Pathogens, 2014Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Tiago Antonio De Oliveira Mendes, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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REVIEW Open Access
2013Co-Authors: Patrick Driguez, Denise L Doolan, Phillip L Felgner, Alex Loukas, Donald P McmanusAbstract:The recent publication of the Schistosoma japonicum and S. mansoni genomes has expanded greatly the opportunities for post-genomic schistosomiasis vaccine research. Immunomics protein microarrays provide an excellent application of this new schistosome sequence information, having been utilised successfully for vaccine antigen discovery with a range of bacterial and viral pathogens, and malaria. Accordingly, we have designed and manufactured a Schistosoma Immunomics protein microarray as a vaccine discovery tool. The microarray protein selection combined previously published data and in silico screening of available sequences for potential immunogens based on protein location, homology to known protective antigens, and high specificity to schistosome species. Following cloning, selected sequences were expressed cell-free and contact-printed onto nitrocellulose microarrays. The reactivity of microarray proteins with antisera from schistosomiasisexposed/resistant animals or human patients can be measured with labelled secondary antibodies and a laser microarray scanner; highly reactive proteins can be further assessed as putative vaccines. This highly innovative technology has the potential to transform vaccine research for schistosomiasis and other parasitic diseases of humans and animals. Revie
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Novel immunomic technologies for schistosome vaccine development
Parasite immunology, 2012Co-Authors: Hamish E G Mcwilliam, Patrick Driguez, Donald P Mcmanus, David Piedrafita, Els N.t. MeeusenAbstract:SUMMARY Schistosomiasis remains one of the most common human helminthiases, despite the availability of an effective drug against the causative parasites. Drug treatment programmes have several limitations, and it is likely that a vaccine is required for effective control. While decades of vaccine development have seen the discovery and testing of several candidate antigens, none have shown consistent and acceptable high levels of protection. The migrating larval stages are susceptible to immunity, however few larval-specific antigens have been discovered. Therefore, there is a need to identify novel larval-specific antigens, which may prove to be more efficacious than existing targets. Immunomics, a relatively new field developed to cope with the recent large influx of biological information, holds promise for the discovery of vaccine targets, and this review highlights some immunomic approaches to schistosome vaccine development. Firstly, a method to focus on the immune response elicited by the important and vulnerable larval stage is described, which allows a targeted study of the immunome at different tissue sites. Then, two high-throughput arrays are discussed for the identification of protein and carbohydrate antigens. It is anticipated that these approaches will progress vaccine development against the schistosomes, as well as other parasites.
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Schistosomiasis vaccine discovery using Immunomics
Parasites & Vectors, 2010Co-Authors: Patrick Driguez, Denise L Doolan, Phillip L Felgner, Alex Loukas, Donald P McmanusAbstract:The recent publication of the Schistosoma japonicum and S. mansoni genomes has expanded greatly the opportunities for post-genomic schistosomiasis vaccine research. Immunomics protein microarrays provide an excellent application of this new schistosome sequence information, having been utilised successfully for vaccine antigen discovery with a range of bacterial and viral pathogens, and malaria. Accordingly, we have designed and manufactured a Schistosoma Immunomics protein microarray as a vaccine discovery tool. The microarray protein selection combined previously published data and in silico screening of available sequences for potential immunogens based on protein location, homology to known protective antigens, and high specificity to schistosome species. Following cloning, selected sequences were expressed cell-free and contact-printed onto nitrocellulose microarrays. The reactivity of microarray proteins with antisera from schistosomiasis-exposed/resistant animals or human patients can be measured with labelled secondary antibodies and a laser microarray scanner; highly reactive proteins can be further assessed as putative vaccines. This highly innovative technology has the potential to transform vaccine research for schistosomiasis and other parasitic diseases of humans and animals.
Mark S. Pearson - One of the best experts on this subject based on the ideXlab platform.
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Immunomics guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis a biomarker identification study
The Lancet Microbe, 2021Co-Authors: Mark S. Pearson, Denise L Doolan, Bemnet Amare Tedla, Luke Becker, Rie Nakajima, Gebeyaw G Mekonnen, Carla Proietti, Al Jasinskas, Abena S Amoah, Stefanie KnoppAbstract:Summary Background Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field. Methods We did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format. Findings From array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC]serum=0·98 [95% CI 0·95–1·00]; AUCurine=0·96 [0·93–0·99]), and MS3_01370 (AUCserum=0·93 [0·89–0·97]; AUCurine=0·81 [0·72–0·89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0·79 [0·69–0·90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%. Interpretation We identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance. Funding Australian Trade and Investment Commission and Merck Global Health Institute.
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Immunomics guided antigen discovery for praziquantel induced vaccination in urogenital human schistosomiasis
Frontiers in Immunology, 2021Co-Authors: Mark S. Pearson, Bemnet Amare Tedla, Luke Becker, Rie Nakajima, Algis Jasinskas, Takafira Mduluza, Francisca Mutapi, Claude Oeuvray, Beatrice Greco, Javier SotilloAbstract:Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.
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An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2016Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Tiago Mendes, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immun
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an Immunomics approach to schistosome antigen discovery antibody signatures of naturally resistant and chronically infected individuals from endemic areas
PLOS Pathogens, 2014Co-Authors: Soraya Gaze, Patrick Driguez, Denise L Doolan, Donald P Mcmanus, Mark S. Pearson, Angela Trieu, Geoffrey N. Gobert, Maria Victoria Periago, Tiago Antonio De Oliveira Mendes, Rodrigo Correa OliveiraAbstract:Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an Immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas
2014Co-Authors: Faculty Publications Microbiology, Patrick Driguez, Denise L Doolan, Tropical Medicine, Mark S. Pearson, Tiago Mendes, Soraya GazeAbstract:An Immunomics approach to schistosome antigen discovery: Antibody signatures of naturally resistant and chronically infected individuals from endemic areas Soraya Gaz
Viroj Wiwanitkit - One of the best experts on this subject based on the ideXlab platform.
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t cell epitope finding on epha2 for further glioma vaccine development an Immunomics study
Journal of Pediatric Neurosciences, 2011Co-Authors: Viroj WiwanitkitAbstract:Background: Glioma is a deadly neurological tumor. For modern management of glioma, glioma vaccinotherapy is the new concept. Materials and Methods: Based on present biomedical technique, the identification of T-cell epitopes via MHC mapping can help clarify the inter-relationship of tumor and immune system. This process can be performed using advanced immunoinformatics technique. Results: Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2. Conclusion: After complete manipulation on EPHA2 molecules, the five best epitopes were derived.
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cancer Immunomics and application of omics for cancer management
Expert Review of Clinical Immunology, 2007Co-Authors: Viroj WiwanitkitAbstract:Several 'omics' sciences have been launched. The outstanding diversity of immune system components, together with the complexity of the regulatory pathways and network-type interactions, makes immunology a combinatorial science. Cancer immonomics is a branch of Immunomics. The present cancer Immunomics project aims at diagnostics and therapy. Comparative and structural genomics can be applied for understanding the underlying tumorogenesis process. For diagnostic purposes, in order to develop a new marker, gene expression analysis technologies, such as DNA microarray, differential display, cDNA subtraction, serial analysis of gene expression and serological proteome analysis, which enable investigators to obtain comprehensive data with respect to gene expression profiles, are progressing rapidly. For therapeutic purposes, vaccine candidate finding, gene therapy and drug-tumor interaction modeling can be clarified by the advance Immunomics techniques. In this article, the author will present the basic concepts on cancer Immunomics and application for basic study of the pathogenesis, diagnosis and treatment of cancer.
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finding a t cell epitope for a melanoma vaccine by an Immunomics technique
Asian Pacific Journal of Cancer Prevention, 2006Co-Authors: Viroj WiwanitkitAbstract:The identification of tumor-associated T cell epitopes has contributed significantly to the understanding of the interrelationship of tumor and immune system and is instrumental in the development of therapeutic vaccines for the treatment of cancer. Here, the author reports preliminary data from the computation analysis of available Homo sapiens melanoma associate antigen to find potential T-cell epitopes using bioinformatics tool namely MHCPred. Using computational algorithm, we predicted the most potential T cell epitope from known melanoma associated antigen. This data are useful for further vaccine development because these promiscuous peptide binders allows to minimize the total number of predicted epitopes without compromising the population coverage required in the design of multi-epitope vaccines.