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AN IMMUNOMICS APPROACH TO SCHISTOSOME ANTIGEN DISCOVERY: ANTIBODY SIGNATURES OF NATURALLY RESISTANT AND CHRONICALLY INFECTED INDIVIDUALS FROM ENDEMIC AREAS
Jangola, Soraya Torres Gaze et al. | Date Issued: 2014
Author
Jangola, Soraya Torres Gaze
Driguez, Patrick
Pearson, Mark S.
Mendes, Tiago
Doolan, Denise L.
Trieu, Angela
McManus, Donald P.
Gobert, Geoffrey N.
Periago, Maria Victoria
Oliveira, Rodrigo Corrêa de
Cardoso, Fernanda C.
Oliveira, Guilherme Corrêa de
Nakajima, Rie
Jasinskas, Al
Hung, Chris
Liang, Li
Pablo, Jozelyn
Bethony, Jeffrey Michael
Felgner, Philip L.
Loukas, Alex
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia.
James Cook University.Australian Institute of Tropical Health and Medicine. Centre for Biodiscovery and Molecular Development of Therapeutics. Queensland Tropical Health Alliance Laboratory Cairns, Queensland, Australia.
Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
QIMR Berghofer Medical Research Institute. Brisbane, Queensland, Australia / The University of Queensland. Institute for Molecular Biosciences. St Lucia, Queensland, Australia.
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.
University of California Irvine. Irvine, CA, USA.
University of California Irvine. Irvine, CA, USA.
University of California Irvine. Irvine, CA, USA.
University of California Irvine. Irvine, CA, USA.
University of California Irvine. Irvine, CA, USA.
George Washington University. Washington, D.C., USA.
University of California Irvine. Irvine, CA, USA.
James Cook University.Australian Institute of Tropical Health and Medicine. Centre for Biodiscovery and Molecular Development of Therapeutics. Queensland Tropical Health Alliance Laboratory Cairns, Queensland, Australia.
Abstract
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.
Keywords
Antibodies
Helminth
Disease Resistance
High-Throughput Screening Assays
Schistosomiasis
Immunology
Epidemiology
 
Publisher
Public Library of Science
Citation
GAZE, Soraya Torres et al. An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas. PLoS Pathogens, v. 10, n. 3, p. 1-16, 2014.
DOI
10.1371/journal.ppat.1004033
ISSN
1553-7366