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T-Helper-2 Cytokine Responses to Sj97 Predict Resistance to Reinfection with Schistosoma japonicum

Tjalling Leenstra,^1,2* Luz P. Acosta,³ Hai-Wei Wu,^1, Gretchen C. Langdon,¹ Julie S. Solomon,¹ Daria L. Manalo,³ Li Su,⁵ Mario Jiz,³ Blanca Jarilla,³ Archie O. Pablo,³ Stephen T. McGarvey,¹ Remigio M. Olveda,³ Jennifer F. Friedman,^1,2 and Jonathan D. Kurtis^1,4

Center for International Health Research,¹ Center for Statistical Sciences, Brown University,⁵ Department of Pediatrics,² Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, Rhode Island,⁴ Department of Immunology, Research Institute for Tropical Medicine, Department of Health, Manila, The Philippines³

Received 24 August 2005/ Returned for modification 6 October 2005/ Accepted 18 October 2005

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-), IL-5/IFN-, and IL-13/IFN-, 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.

Editor: W. A. Petri, Jr.

Present address: Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.

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