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Abstract
The present study evaluated the impact of blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) activity on the protective effect elicited by the fatty acid binding protein (FABP) vaccine against Schistosoma japonicum infection. Mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), FABP, and combination (anti-CTLA-4 mAb and FABP) groups. An assessment of the S. japonicum worm and egg burden in the infected mice revealed that the worm reduction-rate induced by FABP administration was increased from 26.58 to 54.61% by co-administration of the monoclonal anti-CTLA antibody (anti-CTLA-4 mAb). Furthermore, the regulatory T cell (Treg) percentage was significantly increased in mice after administration of the anti-CTLA-4 mAb, but not the FABP vaccine, and elevated levels of the cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-5 were observed in infected mice that were administered the anti-CTLA-4 mAb. Notably, the diameter of egg granulomas in the anti-CTLA-4 mAb and combination groups was significantly increased compared to that observed in the infected control group. Together, these results suggest that co-administering the FABP vaccine and anti-CTLA-4 treatment may have synergistically increased the immunoprotective effect of the FABP vaccine by promoting T-helper 1-type immune responses, while incurring increased tissue damage.
Highlights
Schistosomiasis is a fatal disease that is caused by Schistosoma trematode infections, which incurs negative health and economic effects
The results of this analysis demonstrated that the worm and egg burdens displayed by the fatty acid binding protein (FABP) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody (mAb) groups were significantly reduced compared to those exhibited by mice in the infected control group
Treg CTLA-4 expression has been shown to be upregulated in patients infected with Plasmodium vivax, and the level of CD4+CD25+forkhead box protein 3 (Foxp3)+CTLA4+ T cells after P. vivax infection has been shown to be proportional to the host parasite load [24]
Summary
Schistosomiasis is a fatal disease that is caused by Schistosoma trematode infections, which incurs negative health and economic effects. The FABP derived from F. hepatica has been reported to exert a strong protective effect against S. mansoni infection [4], and a recombinant S. mansoni FABP-pcDNAI plasmid was previously reported to elicit a high level of smFABP-IgG antibody production, and to cause a strong (74.2%) decrease in the number of adult worms, as well as the number of eggs and granulomas [5]. Previous research has confirmed that the inadequate immune protection provided by the (gluthatione-S-transferase) GST vaccine may be the result of vaccine-induced Treg production; the antiCD25 monoclonal antibody (mAb) and cimetidine have been shown to improve the efficacy of the GST vaccine by blocking and reducing the percentage of Tregs, respectively [8, 9]
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