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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Autores principales:	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, Rie Nakajima, Al Jasinskas, Chris Hung, Li Liang, Jozelyn Pablo, Jeffrey M Bethony, Philip L Felgner, Alex Loukas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ae73e03bc4144d068e71898b26df6950
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spelling	oai:doaj.org-article:ae73e03bc4144d068e71898b26df69502021-11-18T06:06:47ZAn immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.1553-73661553-737410.1371/journal.ppat.1004033https://doaj.org/article/ae73e03bc4144d068e71898b26df69502014-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24675823/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Schistosomiasis 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.Soraya GazePatrick DriguezMark S PearsonTiago MendesDenise L DoolanAngela TrieuDonald P McManusGeoffrey N GobertMaria Victoria PeriagoRodrigo Correa OliveiraFernanda C CardosoGuilherme OliveiraRie NakajimaAl JasinskasChris HungLi LiangJozelyn PabloJeffrey M BethonyPhilip L FelgnerAlex LoukasPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 3, p e1004033 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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 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.
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
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 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 Rie Nakajima Al Jasinskas Chris Hung Li Liang Jozelyn Pablo Jeffrey M Bethony Philip L Felgner Alex Loukas
author_sort	Soraya Gaze
title	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_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_sort	immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ae73e03bc4144d068e71898b26df6950
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An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.

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