title: T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum.
abstract: Although schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses to Schistosoma japonicum soluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, where S. japonicum is endemic. S. japonicum transmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-gamma), IL-5/IFN-gamma, and IL-13/IFN-gamma, in response to SWAP predicted a 1.4- to 2.9-month longer time to reinfection (P < 0.05) and a 27 to 55% lower intensity of reinfection (P < 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6- to 2.2-month longer time to reinfection (P < 0.05) and a 30 to 41% lower intensity of reinfection (P < 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P = 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance to S. japonicum and support Sj97 as a leading vaccine candidate for this parasite.
authors.affiliation: Center for International Health Research, Brown University Medical School, 55 Claverick St., Providence, RI 02903, USA. Tjalling_Leenstra@Brown.edu
authors.forename: Tjalling
authors.initials: T
authors.lastname: Leenstra
authors.forename: Luz P
authors.initials: LP
authors.lastname: Acosta
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Wu
authors.forename: Gretchen C
authors.initials: GC
authors.lastname: Langdon
authors.forename: Julie S
authors.initials: JS
authors.lastname: Solomon
authors.forename: Daria L
authors.initials: DL
authors.lastname: Manalo
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Mario
authors.initials: M
authors.lastname: Jiz
authors.forename: Blanca
authors.initials: B
authors.lastname: Jarilla
authors.forename: Archie O
authors.initials: AO
authors.lastname: Pablo
authors.forename: Stephen T
authors.initials: ST
authors.lastname: McGarvey
authors.forename: Remigio M
authors.initials: RM
authors.lastname: Olveda
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Friedman
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014020:Tissue Extracts; D014867:Water
chemical_list: D016207:Cytokines; D014020:Tissue Extracts; D014867:Water