Abstract
A vaccine against schistosomiasis would contribute to a long-lasting decrease in disease spectrum and transmission. Our previous protection studies in mice using Schistosoma mansoni Cathepsin B (Sm-Cathepsin B) resulted in 59 and 60% worm burden reduction with CpG oligodeoxynucleotides and Montanide ISA720 VG as adjuvants, respectively. While both formulations resulted in significant protection in a mouse model of schistosomiasis, the elicited immune responses differed. Therefore, in this study, we aimed to decipher the mechanisms involved in Sm-Cathepsin B vaccine-mediated protection. We performed in vitro killing assays using schistosomula stage parasites as targets for lung-derived leukocytes and serum obtained from mice immunized with Sm-Cathepsin B adjuvanted with either Montanide ISA 720 VG or CpG and from non-vaccinated controls. Lung cells and immune sera from the Sm-Cathepsin B + Montanide group induced the highest killing (63%) suggesting the importance of antibodies in cell-mediated parasite killing. By contrast, incubation with lung cells from Sm-Cathepsin B + CpG immunized animals induced significant parasite killing (53%) independent of the addition of immune serum. Significant parasite killing was also observed in the animals immunized with Sm-Cathepsin B alone (41%). For the Sm-Cathepsin B + Montanide group, the high level killing effect was lost after the depletion of CD4+ T cells or natural killer (NK) cells from the lung cell preparation. For the Sm-Cathepsin B + CpG group, high parasite killing was lost after CD8+ T cell depletion, and a reduction to 39% was observed upon depletion of NK cells. Finally, the parasite killing in the Sm-Cathepsin B alone group was lost after the depletion of CD4+ T cells. Our results demonstrate how the different Sm-Cathepsin B formulations influence the immune mechanisms involved in parasite killing and protection against schistosomiasis.
Highlights
Schistosomiasis is one of the most important human parasitic infections
The experimental vaccine formulation of Sm-Cathepsin B and Montanide ISA 720 VG was compared to the saline control and the Montanide adjuvant control
An antibody-dependent cell-mediated cytotoxicity (ADCC) effect may explain the mechanism of protection in mice vaccinated with Sm-Cathepsin B and Montanide ISA 720 VG
Summary
Schistosomiasis is one of the most important human parasitic infections. The number of infected individuals surpasses 200 million, and this number may be an underestimate of the true infection burden [1]. The MDA programs’ impact on disease transmission has often been questioned, and field studies in Kenya have shown no evidence of an overall reduction in schistosome transmission after several rounds of praziquantel treatment [4]. Maintained disease transmission is a problem for phenotypically susceptible individuals [5] who do not acquire resistance to reinfection after multiple rounds of treatment. The possibility of praziquantel resistant parasite emergence has been discussed for years [6,7,8,9,10] and represents a valid concern as schistosomiasis treatment relies on this one drug. A multifaceted approach to schistosomiasis control that would include drug treatment, snail control, water sanitation, hygiene education, and better disease mapping is suggested [1, 11]. The development of an anti-schistosome vaccine would significantly improve schistosomiasis control efforts, especially if it would be incorporated within this multifaceted approach
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