T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum.
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.
Leenstra
Tjalling
T
Center for International Health Research, Brown University Medical School, 55 Claverick St., Providence, RI 02903, USA. Tjalling_Leenstra@Brown.edu
Acosta
Luz P
LP
Wu
Hai-Wei
HW
Langdon
Gretchen C
GC
Solomon
Julie S
JS
Manalo
Daria L
DL
Su
Li
L
Jiz
Mario
M
Jarilla
Blanca
B
Pablo
Archie O
AO
McGarvey
Stephen T
ST
Olveda
Remigio M
RM
Friedman
Jennifer F
JF
Kurtis
Jonathan D
JD
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
D016207:Cytokines; D014020:Tissue Extracts; D014867:Water