title: An immunomics approach to schistosome antigen discovery: antibody signatures of naturally resistant and chronically infected individuals from endemic areas.
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.
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland, Australia; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Instituto Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Soraya
authors.initials: S
authors.lastname: Gaze
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Driguez
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Pearson
authors.affiliation: Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Mendes
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Trieu
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Instituto Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Periago
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Instituto Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa Oliveira
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Institute for Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Cardoso
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Instituto Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Al
authors.initials: A
authors.lastname: Jasinskas
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Hung
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Jozelyn
authors.initials: J
authors.lastname: Pablo
authors.affiliation: George Washington University, Washington, D.C., United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
authors.affiliation: University of California Irvine, Irvine, California, United States of America.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, Queensland Tropical Health Alliance Laboratory, James Cook University, Cairns, Queensland, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000293:Adolescent; D000328:Adult; D000909:Antibodies, Helminth / Q000097:blood* / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D001938:Brazil / Q000453:epidemiology; D002908:Chronic Disease; D016000:Cluster Analysis; D060467:Disease Resistance / Q000276:immunology*; D019353:Endemic Diseases; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D008875:Middle Aged; D058069:Neglected Diseases / Q000276:immunology; D040081:Protein Array Analysis; D012552:Schistosomiasis / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*; D055815:Young Adult
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D014612:Vaccines