An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.
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 th...
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Public Library of Science (PLoS)
2014-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004033&type=printable |
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| author | Soraya Gaze Patrick Driguez Mark S Pearson Tiago Mendes Denise L Doolan Angela Trieu Donald P McManus Geoffrey N Gobert Maria Victoria Periago Rodrigo Correa Oliveira Fernanda C Cardoso Guilherme Oliveira Guilherme Oliveira Rie Nakajima Al Jasinskas Chris Hung Li Liang Jozelyn Pablo Jeffrey M Bethony Philip L Felgner Alex Loukas |
| author_facet | Soraya Gaze Patrick Driguez Mark S Pearson Tiago Mendes Denise L Doolan Angela Trieu Donald P McManus Geoffrey N Gobert Maria Victoria Periago Rodrigo Correa Oliveira Fernanda C Cardoso Guilherme Oliveira Guilherme Oliveira Rie Nakajima Al Jasinskas Chris Hung Li Liang Jozelyn Pablo Jeffrey M Bethony Philip L Felgner Alex Loukas |
| author_sort | Soraya Gaze |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae73e03bc4144d068e71898b26df6950 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2014-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-ae73e03bc4144d068e71898b26df69502025-08-20T03:01:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-03-01103e100403310.1371/journal.ppat.1004033An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.Soraya GazePatrick DriguezMark S PearsonTiago MendesDenise L DoolanAngela TrieuDonald P McManusGeoffrey N GobertMaria Victoria PeriagoRodrigo Correa OliveiraFernanda C CardosoGuilherme OliveiraGuilherme OliveiraRie NakajimaAl JasinskasChris HungLi LiangJozelyn PabloJeffrey M BethonyPhilip L FelgnerAlex LoukasSchistosomiasis 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004033&type=printable |
| spellingShingle | Soraya Gaze Patrick Driguez Mark S Pearson Tiago Mendes Denise L Doolan Angela Trieu Donald P McManus Geoffrey N Gobert Maria Victoria Periago Rodrigo Correa Oliveira Fernanda C Cardoso Guilherme Oliveira Guilherme Oliveira Rie Nakajima Al Jasinskas Chris Hung Li Liang Jozelyn Pablo Jeffrey M Bethony Philip L Felgner Alex Loukas An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. PLoS Pathogens |
| title | An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. |
| title_full | An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. |
| title_fullStr | An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. |
| title_full_unstemmed | An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. |
| title_short | An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas. |
| title_sort | immunomics approach to schistosome antigen discovery antibody signatures of naturally resistant and chronically infected individuals from endemic areas |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004033&type=printable |
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