A vaccine consisting of Schistosoma mansoni cathepsin B formulated in Montanide ISA 720 VG induces high level protection against murine schistosomiasis.

Alessandra Ricciardi,Momar Ndao,Kittipos Visitsunthorn,John P Dalton

doi:10.1186/s12879-016-1444-z

Abstract

BackgroundSchistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission.MethodOur group has chosen Schistosoma mansoni (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels.ResultsThe Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (P = 0.0002, P < 0.0001, P = 0.0009, respectively). Immunizations with the vaccine elicited robust production of Sm-cathepsin B specific antibodies (endpoint titers = 122,880). Both antigen-specific IgG1 and IgG2c titers were observed, with the former having more elevated titers. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, secreted higher levels of key Th1 cytokines, IFN-γ, IL-12, and TNF-α, as well as the Th2 cytokines IL-5 and IL-4 when stimulated with recombinant Sm-cathepsin B. The Th17 cytokine IL-17, the chemokine CCL5, and the growth factor GM-CSF were also significantly increased in the immunized animals compared to the controls.ConclusionThe formulation tested in this study was able to significantly reduce all forms of parasite burden, stimulate robust production of antigen-specific antibodies, and induce a mixed Th1/Th2 response. These results highlight the potential of Sm-cathepsin B/Montanide ISA 720 VG as a vaccine candidate against schistosomiasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1444-z) contains supplementary material, which is available to authorized users.

Highlights

Schistosomiasis is the most important human helminth infection due to its impact on public health
Hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (P = 0.0002, P < 0.0001, P = 0.0009, respectively)
We report that an immunization regimen involving a formulation of recombinant Smcathepsin B and Montanide ISA 720 VG can significantly reduce worm and egg burdens

Summary

Introduction

Schistosomiasis is the most important human helminth infection due to its impact on public health. It has long been argued that the schistosomiasis disease burden is greatly underestimated, and it has been suggested that the number of infected individuals surpasses 400 million [4]. This underestimation is likely due to the inability of current diagnostic methods to detect light infections. It has been shown that less than 5 % of the schistosomiasis affected population is treated with praziquantel, indicating that control programs are not reaching sufficient coverage [9]. These mass drug administration programs are not sustainable because praziquantel does not prevent re-infection. It has been stated that even a partially effective anti-schistosome vaccine could significantly help accelerate the elimination of schistosomiasis if incorporated with other control efforts such as mass drug administration, intermediate host control, and improved sanitation [11, 12]

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