Abstract
BackgroundImproved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment.MethodologyBlood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously.Principal FindingsA combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10–12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4–9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles.Conclusions/SignificanceIn areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations.
Highlights
Over 200 million people in 74 countries are currently infected with Schistosoma spp. parasites, which are responsible for an estimated 15, 000 deaths and 1.76 million disability adjusted life years per annum [1,2,3]
S. haematobium infection distribution in the study cohort The baseline study cohort consisted of 94 males and 101 females ranging in age from 4–84 years
The latter is the case for innate inflammatory, regulatory and Th17 associated immune markers due to the relatively recent characterisation of the role played by these immune phenotypes in human schistosomiasis [10,49,50]
Summary
Over 200 million people in 74 countries are currently infected with Schistosoma spp. parasites, which are responsible for an estimated 15, 000 deaths and 1.76 million disability adjusted life years per annum [1,2,3]. Since PZQ does not prevent reinfection, an anti-schistosome vaccine based on the Schistosoma haematobium enzyme glutathione-S-transferase (GST) is being developed. Our study suggests that current and future GST-based vaccine trials should take host age, schistosome infection status and PZQ treatment history into account since these factors influence GST-specific immune activation. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment
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