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Infection and Immunity, May 2009, p. 2051-2058, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.00012-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Immunoglobulin E (IgE) Responses to Paramyosin Predict Resistance to Reinfection with Schistosoma japonicum and Are Attenuated by IgG4{triangledown}

Mario Jiz,1 Jennifer F. Friedman,1,2 Tjalling Leenstra,1 Blanca Jarilla,3 Archie Pablo,3 Gretchen Langdon,1 Sunthorn Pond-Tor,1 Hai-Wei Wu,1,2 Daria Manalo,3 Remigio Olveda,3 Luz Acosta,3 and Jonathan D. Kurtis1,4*

Center for International Health Research, Rhode Island Hospital, Providence, Rhode Island,1 Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island,2 Research Institute for Tropical Medicine, Manila, the Philippines,3 Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, Rhode Island4

Received 5 January 2009/ Returned for modification 10 February 2009/ Accepted 28 February 2009

Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatment-based control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n = 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P = 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n = 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n = 274), even after adjusting for potential confounders (P = 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.

* Corresponding author. Mailing address: Center for International Health Research, Rhode Island Hospital, 55 Claverick Street, Providence, RI 02901. Phone: (401) 444-7375. Fax: (401) 444-7854. E-mail: Jonathan_Kurtis{at}Brown.edu

{triangledown} Published ahead of print on 9 March 2009.

Editor: J. F. Urban, Jr.

Infection and Immunity, May 2009, p. 2051-2058, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.00012-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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