T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum

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

Research output: Contribution to journalArticle

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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-γ), IL-5/IFN-γ, and IL-13/IFN-γ, 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.

Original languageEnglish (US)
Pages (from-to)370-381
Number of pages12
JournalInfection and Immunity
Volume74
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Schistosoma japonicum
Interleukin-5
Interleukin-12
Cytokines
Praziquantel
Interleukin-13
Interleukin-4
Parasites
Vaccines
Philippines
Schistosomiasis
Interleukin-10
Population
Therapeutics
Morbidity
Drug Therapy

ASJC Scopus subject areas

  • Immunology

Cite this

Leenstra, T., Acosta, L. P., Wu, H. W., Langdon, G. C., Solomon, J. S., Manalo, D. L., ... Kurtis, J. D. (2006). T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum. Infection and Immunity, 74(1), 370-381. https://doi.org/10.1128/IAI.74.1.370-381.2006

T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum. / Leenstra, Tjalling; Acosta, Luz P.; Wu, Hai Wei; Langdon, Gretchen C.; Solomon, Julie S.; Manalo, Daria L.; Su, Li; Jiz, Mario; Jarilla, Blanca; Pablo, Archie O.; McGarvey, Stephen T.; Olveda, Remigio M.; Friedman, Jennifer F.; Kurtis, Jonathan D.

In: Infection and Immunity, Vol. 74, No. 1, 01.2006, p. 370-381.

Research output: Contribution to journalArticle

Leenstra, T, Acosta, LP, Wu, HW, Langdon, GC, Solomon, JS, Manalo, DL, Su, L, Jiz, M, Jarilla, B, Pablo, AO, McGarvey, ST, Olveda, RM, Friedman, JF & Kurtis, JD 2006, 'T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum', Infection and Immunity, vol. 74, no. 1, pp. 370-381. https://doi.org/10.1128/IAI.74.1.370-381.2006
Leenstra, Tjalling ; Acosta, Luz P. ; Wu, Hai Wei ; Langdon, Gretchen C. ; Solomon, Julie S. ; Manalo, Daria L. ; Su, Li ; Jiz, Mario ; Jarilla, Blanca ; Pablo, Archie O. ; McGarvey, Stephen T. ; Olveda, Remigio M. ; Friedman, Jennifer F. ; Kurtis, Jonathan D. / T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum. In: Infection and Immunity. 2006 ; Vol. 74, No. 1. pp. 370-381.
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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-γ), IL-5/IFN-γ, and IL-13/IFN-γ, 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.",
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