title: Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.
abstract: Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University , Cairns, QLD , Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Pearson
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University , Cairns, QLD , Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Becker
authors.affiliation: QIMR Berghofer Medical Research Institute , Brisbane, QLD , Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Driguez
authors.affiliation: University of Melbourne , Melbourne, VIC , Australia.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Young
authors.affiliation: Centro de Pesquisas Rene Rachou, Oswaldo Cruz Foundation , Belo Horizonte , Brazil.
authors.forename: Soraya
authors.initials: S
authors.lastname: Gaze
authors.affiliation: Federal University of Minas Gerais , Belo Horizonte , Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Mendes
authors.affiliation: National Institute of Parasitic Diseases , Shanghai , China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: QIMR Berghofer Medical Research Institute , Brisbane, QLD , Australia.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
authors.affiliation: National Institutes of Health Research , Harare , Zimbabwe.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Midzi
authors.affiliation: Department of Biochemistry, University of Zimbabwe , Harare , Zimbabwe.
authors.forename: Takafira
authors.initials: T
authors.lastname: Mduluza
authors.affiliation: QIMR Berghofer Medical Research Institute , Brisbane, QLD , Australia.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.affiliation: Department of Biology, University of York , York , UK.
authors.forename: R Alan
authors.initials: RA
authors.lastname: Wilson
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University , Washington, DC , USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
authors.affiliation: University of Edinburgh , Edinburgh , UK.
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.affiliation: University of Edinburgh , Edinburgh , UK.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mutapi
authors.affiliation: University of California Irvine , Irvine, CA , USA.
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, James Cook University , Cairns, QLD , Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
keywords: drug-induced resistance; human; protein microarray; schistosomiasis; vaccine