Schistosoma mansoni egg-derived extracellular vesicles: A promising vaccine candidate against murine schistosomiasis

Mossallam, Shereen F.; Abou-El-Naga, Iman F.; Bary, Amany Abdel; Elmorsy, Eman A.; Diab, Radwa G.

doi:10.1371/journal.pntd.0009866

Cited by 15 publications

(8 citation statements)

References 60 publications

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“…The IgG level was found to be much higher in the SLAP and SEA group compared to the infected control group (P<0.001). In a previous report, Mossallam et al [42] agreed with our result, as in their study the combination of alum and Schistosoma's extracellular vesicles (EVs) led to considerably greater antibody levels at all various research time points. In comparison to subgroups of infected controls, IgG levels were considerably raised by immunization with or without adjuvant.…”

Section: Discussionsupporting

confidence: 92%

Immunological evaluation of the prophylactic impact of soluble egg antigen (SEA) combined with schistosomula lung antigen preparation (SLAP) on murine model of schistosomiasis mansoni

Elkholy

soliman²,

elawady³

et al. 2022

Parasitologists United Journal

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Background: Vaccination against schistosomiasis might be an excellent approach for its control and elimination. Despite the recent advances in identification of several potential vaccine candidates, no vaccine was validated for clinical trials.Objective: This research aims to evaluate the preventive effects of soluble egg antigen (SEA) in combination with schistosomula lung antigen preparation (SLAP) on a murine model of schistosomiasis mansoni. Material and Methods: In this study, 35 Swiss albino male mice (aged 6 to 8 weeks) were divided into five groups. Each group contained seven mice, with G1 serving as the normal control, G2 the infected control, G3 the infected and immunized by SEA, G4 the infected and immunized by SLAP, and G5 the infected and immunized by combination antigens (SLAP and SEA). All mice were infected two weeks after receiving their final dose of immunization. Seven weeks following infection, mice were decapitated in order to determine the impact of the injected antigens using determination of liver enzymes, IL10, TNF-α and schistosomal IgG, with immunohistochemical assessment. Results: Reduced liver enzyme levels were detected in various vaccinated groups, with the combined group (SLAP and SEA) experiencing the greatest reduction. The combination of SLAP and SEA resulted in the highest significant increase in IL-10 and IgG antibody and the highest significant reduction in TNF-α level among all groups. Conclusion:The combination of SLAP and SEA increased the protective immunity. This combination represents an exciting direction in vaccine research.

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Section: Discussionsupporting

confidence: 92%

Immunological evaluation of the prophylactic impact of soluble egg antigen (SEA) combined with schistosomula lung antigen preparation (SLAP) on murine model of schistosomiasis mansoni

Elkholy

soliman²,

elawady³

et al. 2022

Parasitologists United Journal

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“…Mice infection: S. mansoni cercariae were inoculated and infected subcutaneously with 60 ± 10 strain of Egyptian S . mansoni cercariae sheds from Biomphalaria alexandrina snail in accordance to Mossallam et al [ 33 ].…”

Section: Methodssupporting

confidence: 87%

“…Additionally, the anti-calpain-engineered lipoidal nanosystem, when compared with the same dose of PZQ, showed a greater effect on both the mature and immature ova, as well as caused ova dead during the egg developmental stages in both the young and adult worm represented by two weeks and four weeks post-infected mice, respectively. The calculation of the reduction in the total worm burden, egg developmental stages, the number of eggs/gram tissue and the percentage of reduction in total ova/gram tissue is the criteria for parasitological cure rate [ 33 , 34 , 35 ]. These enormous effects of the anti-calpain-engineered nanoliposomes on schistosomes eggs, and worms may be due to the target rate and greater absorption of the nanosystem by the worms and the eggs in the liver, porto-mesenteric, and intestine.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Evaluation of an Antibody-Functionalized Lipoidal Nanosystem for Schistosomiasis Intervention

Adekiya

Kumar²,

Kondiah³

et al. 2022

Pharmaceutics

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This study employed nanotechnological techniques to design and develop a praziquantel nanoliposomal (NLP) system and surface-functionalized the NLP with anti-calpain antibody (anti-calpain-NLP) for targeted praziquantel (PZQ) delivery in the treatment of schistosomiasis. Anti-calpain-NLPs were prepared and validated for their physicochemical parameters, in vitro and in vivo toxicity, drug entrapment efficiency (DEE), drug loading capacity (DLC), drug release, and parasitological cure rate. The particle sizes for the formulated nanoliposomes ranged from 88.3 to 92.7 nm (PDI = 0.17–0.35), and zeta potential ranged from −20.2 to −31.9 mV. The DLC and DEE ranged from 9.03 to 14.16 and 92.07 to 94.63, respectively. The functionalization of the nanoliposome surface was stable, uniform, and spherical. Fourier-transform infrared (FTIR), thermal behavior and X-ray powder diffraction (XRPD) analysis confirmed that the anti-calpain antibody and PZQ were attached to the surface and the nanoliposomes inner core, respectively. The drug sustained release was shown to be 93.2 and 91.1% within 24 h for NLP and anti-calpain-NLP, respectively. In the in vitro analysis study, the nanoliposome concentrations range of 30 to 120 μg/mL employed revealed acceptable levels of cell viability, with no significant cytotoxic effects on RAW 264.7 murine macrophage as well as 3T3 human fibroblast cells. Biochemical markers and histopathological analysis showed that the formulated nanoliposomes present no or minimal oxidative stress and confer hepatoprotective effects on the animals. The cure rate of the anti-calpain-NLP and PZQ was assessed by parasitological analysis, and it was discovered that treatment with 250 mg/kg anti-calpain-NLP demonstrated greater activity on the total worm burden, and ova count for both the juvenile and adult schistosomes in the intestine and liver of infected mice. The findings so obtained supported the ability of oral anti-calpain-NLP to target young and adult schistosomes in the liver and porto-mesenteric locations, resulting in improved effectiveness of PZQ.

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“…Adult worms are obtained from perfusion of the portal venous system of mice or hamsters infected with cercarial larvae, and eggs can be isolated from enzymatically digested liver and gut tissue from the infected animals. EVs are released by all three life stages as part of the complex excretory/secretory (E/S) products released by S. mansoni [17][18][19]. Studying their EVs requires separation from other proteins and lipids in these E/S products.…”

Section: Introductionmentioning

confidence: 99%

Optimized Protocol for the Isolation of Extracellular Vesicles from the Parasitic Worm Schistosoma mansoni with Improved Purity, Concentration, and Yield

Kuipers

Koning

Bos

et al. 2022

Journal of Immunology Research

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In the past decade, the interest in helminth-derived extracellular vesicles (EVs) increased owing to their role in pathogen-host communication. However, the availability of EVs from these parasitic worms is often limited due to the restricted occurrence and culturing possibilities of these organisms. Schistosoma mansoni is one of several helminths that have been shown to release EVs affecting the immune response of their host. Further investigation of mechanisms underlying these EV-induced effects warrants separation of EVs from other components of the helminth excretory/secretory products. However, isolation of high-purity EVs often come to the expense of reduced EV yield. We therefore aimed to develop an optimized protocol for isolation of EVs from S. mansoni schistosomula and adult worms with respect to purity, concentration, and yield. We tested the use of small (1.7 ml) iodixanol density gradients and demonstrated that this enabled western blot-based analysis of the EV marker protein tetraspanin-2 (TSP-2) in gradient fractions without additional concentration steps. Moreover, the concentration and yield of EVs obtained with small iodixanol gradients were higher compared to medium-sized (4.3 ml) or conventional large-sized (12 ml) gradients. Additionally, we provide evidence that iodixanol is preferred over sucrose as medium for the small density gradients, because EVs in iodixanol gradients reached equilibrium much faster (2 hours) and iodixanol but not sucrose was suitable for purification of schistosomula EVs. Finally, we demonstrate that the small iodixanol gradients were able to separate adult worm EVs from non-EV contaminants such as the blood digestion product hemozoin. Our optimized small iodixanol density gradient allows to simultaneously separate and concentrate EVs while reducing handling time and EV loss and can be applied for EVs from helminths and other limited EV sources.

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Schistosoma mansoni egg-derived extracellular vesicles: A promising vaccine candidate against murine schistosomiasis

Cited by 15 publications

References 60 publications

Immunological evaluation of the prophylactic impact of soluble egg antigen (SEA) combined with schistosomula lung antigen preparation (SLAP) on murine model of schistosomiasis mansoni

Immunological evaluation of the prophylactic impact of soluble egg antigen (SEA) combined with schistosomula lung antigen preparation (SLAP) on murine model of schistosomiasis mansoni

In Vivo Evaluation of an Antibody-Functionalized Lipoidal Nanosystem for Schistosomiasis Intervention

Optimized Protocol for the Isolation of Extracellular Vesicles from the Parasitic Worm Schistosoma mansoni with Improved Purity, Concentration, and Yield

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