Immunoprophylaxical potential of a Schistosoma Mansoni Cercarial Protease

یک پروتئاز سرکر شیستوزوما مانسونی مورد شناسایی قرار گرفت. وزن مولکولی این آنزیم 27kDa تعیین گردید و مطالعات بعدی نشان داد که فعالیت پروتئولیتیک آن با (Phenylmethanesulfonyl fluoride=PMSF) از بین می رود، یعنی اینکه آنزیم مورد نظر یک سرین پروتئاز است. بمنظور بررسی اثر ایمنو پروفیلاکسی آنزیم فوق 18 موش آزمایشگاهی CBA با مخلوطی که پروتئاز سرکر اصلی ترین قسمت آن بود واکسینه شدند. سپس موش های فوق و موش های CBA گروه شاهد که فقط با ادجونت تزریق شده بودند به شیستوزوما مانسونی آلوده گردیدند. نهایتا همه موش ها کشته شدند و تعداد کرم موجود در عروق خونی و تعداد تخم موجود در یک گرم کبد هر موش شمارش گردید. نتایج این بررسی نشان داد که 5 موش از تعداد کل 18 موش مورد آزمایش علیه آنزیم فوق تولید آنتی بادی نمودند اما موش هایی که ضد این پروتئاز آنتی بادی تولید نمودند به صورت معنی داری در مقایسه با گروه شاهد نسبت به آلودگی به شیستوزوما مانسونی مصون شده بودند. در نتیجه به نظر می رسد در صورتی که به طریقی خاصیت ایمینوژنیسیتی آنزیم پروتئاز سرکر شیستوزوما افزایش داده شود این ماده می تواند به عنوان واکسن علیه شیستوزومیازیس مطرح شود

Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development.

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host-parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen

Multivariable regression analysis in Schistosoma mansoni-infected individuals in the Sudan reveals unique immunoepidemiological profiles in uninfected, egg+ and non-egg+ infected individuals

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in schoolaged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals(range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles(cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals

Comparison of Schistosoma mansoni Soluble Cercarial Antigens and Soluble Egg Antigens for Serodiagnosing Schistosome Infections

A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid – SmCTF) was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA) in an indirect enzyme-immunoassay (ELISA) antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA) in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis

Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development.

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host-parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen

NMU: reactivity of sera from the Peoples Republic of China against <i>S. mansoni</i> SEA (SmSEA), <i>S. japonicum</i> SEA (SjSEA) and <i>S. mansoni</i> CTF (SmCTF) in ELISA.

<p>Twenty five sera were from <i>S. japonicum</i> egg-positive subjects and 17 from egg-negative subjects, both groups living in an area endemic for schistosomiasis japonicum, and 20 sera from negative controls living outwith an endemic area. Horizontal lines indicate the mean OD450 values for each antigen in each of the subject groups. • SmSEA ▪ SjSEA ▴ SmCTF.</p

AMC: correlation between <i>S. mansoni</i> cercarial transformation fluid (SmCTF) and soluble egg antigen (SmSEA) in ELISA.

<p>Results for sera from a total of 46 subjects: 21 from patients with parasitologically-proven schistosome infections, 20 sera that were positive in routine serology and 5 negative controls. □ = sera from patients known to be <i>S. mansoni</i>-infected; ○ = sera from patients known to be <i>S. haematobium</i>-infected; ▪ = sera from patients with Katayama fever; • = sera from patients that tested positive for schistosomiasis in routine serology, but were egg-negative; ▴ = control negative sera from patients that tested negative in routine serology.</p

SPDRL: correlation between <i>S. mansoni</i> cercarial transformation fluid (SmCTF) and soluble egg antigen (SmSEA) in ELISA.

<p>Results for sera from 8 subjects previously shown parasitologically to be infected with <i>S. haematobium</i> and 8 subjects suspected to be infected with <i>S. haematobium</i>. ▴ = 2 positive and 6 negative sera from patients that had visited Lake Malawi; □ = patients with <i>S. haematobium</i> eggs in urine; ▪ = control positive sera from patients known to be <i>S. haematobium</i>-infected.</p