title: Cytokine responses to the anti-schistosome vaccine candidate antigen glutathione-S-transferase vary with host age and are boosted by praziquantel treatment.
abstract: BACKGROUND
  Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.
  
  
  METHODS
  Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.
  
  
  RESULTS
  A combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10-12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4-9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.
  
  
  CONCLUSIONS
  In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations.
authors.affiliation: Institute of Immunology & Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Claire D
authors.initials: CD
authors.lastname: Bourke
authors.affiliation: Institute of Immunology & Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.affiliation: Institute of Immunology & Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rujeni
authors.affiliation: Institute of Immunology & Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Appleby
authors.affiliation: Centre d'Infection et d'Immunité de Lille, Inserm U 1019, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Trottein
authors.affiliation: National Institute of Health Research, Harare, Zimbabwe.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Midzi
authors.affiliation: Biochemistry Department, University of Zimbabwe, Harare, Zimbabwe.
authors.forename: Takafira
authors.initials: T
authors.lastname: Mduluza
authors.affiliation: Institute of Immunology & Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mutapi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011223:Praziquantel / Q000627:therapeutic use*; D012548:Schistosoma haematobium / Q000276:immunology*; D012553:Schistosomiasis haematobia / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D012556:Schistosomicides / Q000627:therapeutic use; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology; D055815:Young Adult
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D012556:Schistosomicides; D014612:Vaccines; D011223:Praziquantel; D005982:Glutathione Transferase