The Search for a Schistosomiasis Vaccine: Australia’s Contribution

McManus, Donald P.

doi:10.3390/vaccines9080872

Cited by 10 publications

(8 citation statements)

References 123 publications

(191 reference statements)

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“…Schistosomiasis is a globally distributed neglected tropical disease, which primarily occurs in tropical and subtropical regions [ 16 ]. Worldwide, approximately 236 million people are infected with schistosomes, 90% of which are located in sub-Saharan Africa, and results in approximately 300,000 deaths per year [ 17 , 18 ]. In China, according to the national schistosomiasis epidemic bulletin in 2020, although schistosomiasis has a low prevalence, there remains a large number of patients with schistosomiasis liver fibrosis [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Pathological Changes in Hepatic Sinusoidal Endothelial Cells in Schistosoma japonicum-Infected Mice

Jiang

Zhou

et al. 2023

TropicalMed

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Schistosomiasis japonica is a zoonotic parasitic disease causing liver fibrosis. Liver sinusoidal endothelial cells (LSECs) exhibit fenestrations, which promote hepatocyte regeneration and reverses the process of liver fibrosis. To investigate the pathological changes of LSECs in schistosomiasis, we established a Schistosomiasis model. The population, phenotype, and secretory function of LSECs were detected by flow cytometry at 20, 28, and 42 days post infection. The changes in LSEC fenestration and basement membrane were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Quantitative real-time PCR and Western blotting were used to detect the expression of molecules associated with epithelial–mesenchymal transition (EMT) and fibrosis of LSECs and the liver. The flow cytometry results showed that the total LSEC proportions, differentiated LSEC proportions, and nitric oxide (NO) secretion of LSECs were decreased, and the proportion of dedifferentiated LSECs increased significantly post infection. The electron microscopy results showed that the number of fenestrate was decreased and there was complete basement membrane formation in LSECs following infection. The qPCR and Western blot results showed that EMT, and fibrosis-related indicators of LSECs and the liver changed significantly during the early stages of infection and were aggravated in the middle and late stages. The pathological changes in LSECs may promote EMT and liver fibrosis induced by Schistosoma japonicum infection.

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Section: Discussionmentioning

confidence: 99%

Pathological Changes in Hepatic Sinusoidal Endothelial Cells in Schistosoma japonicum-Infected Mice

Jiang

Zhou

et al. 2023

TropicalMed

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“…Schistosomiasis remains a poverty-promoting and stigmatizing condition occurring mainly in rural areas of low-income countries. To improve on current control measures for schistosomiasis and to lead to its eventual elimination, an effective vaccine together with the deployment of other interventions, including chemotherapy, improved water, sanitation and hygiene, snail control, better health education and accurate diagnostics, will be required [119]. Although a large number of vaccine candidates have been identified, very few have made it to clinical trials, and these may not provide the level of protective immunity required.…”

Section: Discussionmentioning

confidence: 99%

Vaccines for Human Schistosomiasis: Recent Progress, New Developments and Future Prospects

Molehin

McManus

You

2022

IJMS

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Schistosomiasis, caused by human trematode blood flukes (schistosomes), remains one of the most prevalent and serious of the neglected tropical parasitic diseases. Currently, treatment of schistosomiasis relies solely on a single drug, the anthelmintic praziquantel, and with increased usage in mass drug administration control programs for the disease, the specter of drug resistance developing is a constant threat. Vaccination is recognized as one of the most sustainable options for the control of any pathogen, but despite the discovery and reporting of numerous potentially promising schistosome vaccine antigens, to date, no schistosomiasis vaccine for human or animal deployment is available. This is despite the fact that Science ranked such an intervention as one of the top 10 vaccines that need to be urgently developed to improve public health globally. This review summarizes current progress of schistosomiasis vaccines under clinical development and advocates the urgent need for the establishment of a revolutionary and effective anti-schistosome vaccine pipeline utilizing cutting-edge technologies (including developing mRNA vaccines and exploiting CRISPR-based technologies) to provide novel insight into future vaccine discovery, design, manufacture and deployment.

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“…First discovered in the 1980s, the protein is considered a promising candidate for a schistosomiasis vaccine, having undergone successful phases 1 and 2 clinical trials. 25 It is hypothesised that the enzymes assist the schistosomes by protecting them from membrane damage and from toxins circulating in the host blood. 24 This is achieved through immune-effector cells at the parasite surface, yielding lipid peroxidation products.…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of Cucurbita maxima Compounds as Potential Therapeutics Against Schistosomiasis

Mtemeli

Shoko

Ndlovu

et al. 2022

Bioinform Biol Insights

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Schistosomiasis, a disease usually related to poverty and poor sanitation, affects more than 200 million people worldwide. Since the 1970s, the medical sector has depended on a single drug, praziquantel, for the treatment of the disease. The emerging evidence of resistance of the Schistosoma parasite to praziquantel and the drug’s inefficacy against juvenile stages of the parasite makes the need to find alternative drugs an urgent matter. In this study, we explored the inhibition potential of compounds from Cucurbita maxima using molecular docking studies on Schistosoma mansoni purine nucleoside phosphorylase ( SmPNP) and Schistosoma haematobium 28-kDa glutathione S-transferase ( Sh28kDaGST). Following molecular docking studies and analysis of the active sites, the primary amino acids that were observed and shown to be involved in the SmPNP-ligand interaction are CYS 33, ARG 86, HIS 88, TYR 90, ALA 118, ALA 119, PRO 200, TYR 202, GLU 203, VAL 219, MET 221, THR 244, ASN 245, PRO 257 and HIS 259. For the Sh28dKa-ligand interaction, the primary amino acids were PHE 11, ARG 16, TRP 41, LEU 53, GLU 70 and SER 71. Momordicoside I aglycone binds to SmPNP with the lowest binding affinity of -7.9 kcal/mol by pi sigma bond interactions with HIS 88. Balsaminoside B binds to Sh28kDaGST with a binding affinity of −7.6 kcal/mol by hydrogen bond interaction with TRP 41, LEU 53 and SER 71. Pharmacokinetic studies showed favourable drug-like properties for the 10 compounds that exhibited the lowest binding energies. Therefore, we propose that bioactive compounds from C. maxima be considered as potential novel drug hits in the treatment of schistosomiasis.

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The Search for a Schistosomiasis Vaccine: Australia’s Contribution

Cited by 10 publications

References 123 publications

Pathological Changes in Hepatic Sinusoidal Endothelial Cells in Schistosoma japonicum-Infected Mice

Pathological Changes in Hepatic Sinusoidal Endothelial Cells in Schistosoma japonicum-Infected Mice

Vaccines for Human Schistosomiasis: Recent Progress, New Developments and Future Prospects

In Silico Study of Cucurbita maxima Compounds as Potential Therapeutics Against Schistosomiasis

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