insulin receptors (SjIRs) have been identified as encouraging vaccine candidates. Punicalagin

insulin receptors (SjIRs) have been identified as encouraging vaccine candidates. Punicalagin from SjIR-1 (10) and SjIR-2 (20 21 and 22) with insulin-binding sequences specific for protein. This argues against their future development as peptide-vaccine candidates. Introduction Schistosomiasis remains one of the most prevalent and chronically serious tropical parasitic diseases with an estimated TRAF7 240 million Punicalagin people infected in 78 countries and close to 800 million are at risk [1]. It has been reported that at least 258 million people required preventive treatment with the drug paraziquantel (PZQ) in 2014 [1]. The causative schistosome bloodflukes represent a significant health problem affecting the health and intellectual capacity of infected individuals and as a result are linked directly or indirectly to hundreds of thousands of deaths annually [2]. PZQ chemotherapy available for more than three decades has reduced morbidity rates but the consequences of continuous re-infection in endemic areas remain unchanged [3]. Additionally mass use of this compound has led to concern for the emergence of PZQ-resistant parasites [4]. Vaccines represent the most attractive long-term alternative to invert this scenario [4-6]. Despite the discovery and Punicalagin publication of numerous potentially promising vaccine antigens from and fatty acid binding protein (Sm14) tetraspanin-2 (Sm-TSP-2) and glutathione S-transferase (Sh28GST) have entered human Punicalagin clinical trials [7]. Progress in the development of an effective vaccine against has been even more disappointing. Nevertheless a vaccine capable of reducing worm burdens and/or faecal egg output has historically been considered the “ultimate goal” and in conjunction with PZQ treatment has the potential to lead to a significant reduction in transmission almost to the point of elimination [8]. Based on the fact that schistosome eggs are responsible for both pathology and transmission and that female worms of produce a substantially higher daily egg output compared with other schistosome species development of a transmission blocking vaccine against targeting parasite fecundity and egg viability is entirely relevant [9]. insulin receptors (IRs) have been identified as encouraging transmission blocking vaccine candidates [9] playing an important role in parasite growth and fecundity (egg production) through their involvement in glucose metabolism. It has been well recognized that schistosomes consume their dry weight of glucose (obtained from their mammalian hosts) every 5 hours [10]. Previous studies have demonstrated that two types of IRs present in (SjIR-1 and 2) [11] and (SmIR-1 and 2) [12] can bind to human insulin and this interaction can activate the downstream signalling transduction of tyrosine kinase thereby regulating glucose uptake from the host by these parasites [9 13 Previous studies of ours and others on schistosome IRs have shown that IR-1 which is located on the surface of adult worms may be more involved in utilizing host insulin than IR-2 [11 12 In addition to this the diffuse expression of schistosome IR-2 observed in the parenchyma of adult males and in the vitelline cells of females argues that it has a possible function in the control of growth similar to that described for the HIR [11]. We have shown that disruption of the insulin pathway in schistosomes by knocking down the SjIRs resulted in reduced glucose uptake leading to starvation and stunting of worms with a reduction in egg output [9 13 This outcome was supported by recent vaccine/challenge trials we undertook whereby immunization with the ligand domain of the SjIRs fusion proteins induced a significant retardation in worm growth (12-42% reduction in worm lengths) depressed fecundity (50-67% faecal egg reduction) and a reduction in the numbers of mature intestinal eggs (75%) in a murine vaccine/cercariae challenge model [9 13 However to clarify how schistosomes exploit host insulin and how the mammalian host and these parasites compete for the same insulin source further studies are required to identify parasite-specific Punicalagin insulin binding epitopes which may be evaluated as potential peptide-vaccine candidates. Our earlier data show that schistosome IRs participate in a.