The biotechnology-value chain: Development of Sm14 as a schistosomiasis vaccine

Tendler, Míriam; Simpson, Andrew J.G.

doi:10.1016/j.actatropica.2008.09.002

Cited by 78 publications

(50 citation statements)

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“…Parasitic worms possess limited lipid metabolism and depend on import of essential lipids from their host (4), which makes the lipid transporters good targets for chemoprophylactic treatments. A 14-kDa FABP (Sm14) has been proposed as a vaccine candidate against Schistosoma mansoni in humans and Fasciola hepatica in cattle and sheep (5,6). Work with parasitic species, which possess a complex life cycle often involving several hosts, is difficult, and therefore, Caenorhabditis elegans has been proposed as a suitable model organism for studying roundworm diseases and nematode metabolism (7,8).…”

mentioning

confidence: 99%

Fatty Acid- and Retinoid-binding Proteins Have Distinct Binding Pockets for the Two Types of Cargo

Jordanova

Groves

Kostova

et al. 2009

Journal of Biological Chemistry

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Parasitic nematodes cause serious diseases in humans, animals, and plants. They have limited lipid metabolism and are reliant on lipid-binding proteins to acquire these metabolites from their hosts. Several structurally novel families of lipidbinding proteins in nematodes have been described, including the fatty acid-and retinoid-binding protein family (FAR). In Caenorhabditis elegans, used as a model for studying parasitic nematodes, eight C. elegans FAR proteins have been described. The crystal structure of C. elegans FAR-7 is the first structure of a FAR protein, and it exhibits a novel fold. It differs radically from the mammalian fatty acid-binding proteins and has two ligand binding pockets joined by a surface groove. The first can accommodate the aliphatic chain of fatty acids, whereas the second can accommodate the bulkier retinoids. In addition to demonstrating lipid binding by fluorescence spectroscopy, we present evidence that retinol binding is positively regulated by casein kinase II phosphorylation at a conserved site near the bottom of the second pocket. far-7::GFP (green fluorescent protein) expression shows that it is localized in the head hypodermal syncytia and the excretory cell but that this localization changes under starvation conditions. In conclusion, our study provides the basic structural and functional information for investigation of inhibitors of lipid binding by FAR proteins.Hydrophobic lipophilic molecules such as fatty acids, eicosanoids, retinoids, and steroids have important functions both as energy sources and in metabolic signaling. They affect fundamental cellular processes such as gene transcription, cell development, inflammation, and immune response (1-3). The cellular cytosol is hydrophilic, and lipids need to be solubilized and protected from chemical damage. Their transport and availability are tightly regulated. Proteins that coordinate the lipid traffic include lipoproteins (such as the low density lipoprotein) and carrier proteins, known as lipid-binding proteins (LBPs).2 In vertebrates LBPs belong to the ␤-sheet calycin superfamily (lipocalins and fatty acid-binding proteins (FABPs)) or the ␣-helical serum albumin-like superfamily. Nematodes are one of the most abundant groups of multicellular organisms. Parasitic nematodes cause serious and difficult to treat diseases in humans, animals, and plants affecting human health as well as having a negative impact on agricultural economics. It is estimated that more than one-sixth of the earth's population (mainly in developing countries), suffers from nematode infections, and at least 4 of the 15 neglected tropical diseases listed by the World Health Organization are caused by nematodes. Parasitic worms possess limited lipid metabolism and depend on import of essential lipids from their host (4), which makes the lipid transporters good targets for chemoprophylactic treatments. A 14-kDa FABP (Sm14) has been proposed as a vaccine candidate against Schistosoma mansoni in humans and Fasciola hepatica in cattle and sheep (5, ...

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mentioning

confidence: 99%

Fatty Acid- and Retinoid-binding Proteins Have Distinct Binding Pockets for the Two Types of Cargo

Jordanova

Groves

Kostova

et al. 2009

Journal of Biological Chemistry

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“…Other vaccines presented at a recent vaccine discovery workshop sponsored by the Bill and Melinda Gates Foundation in the United States (Kupferschmidt, 2013) identified additional vaccines still in experimental development, including Sm14, a fatty acid binding protein, a calpain (Smp80) from S. mansoni, and Sj23, a TSP, a triose-phosphate isomerase, an insulin receptor, and paramyosin from S. japonicum (Zhu et al, 2004;Siddiqui et al, 2005;Tendler and Simpson, 2008;You et al, 2012). An advantage of vaccination strategies against the zoonotic S. japonicum is that the parasite is found in a variety of domesticated animals, including water buffalo and goats in China.…”

Section: Prevention Of Schistosomiasisvaccinesmentioning

confidence: 99%

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Leow

Willis

Hofmann

et al. 2014

British J Pharmacology

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Neglected tropical diseases are a group of some 17 diseases that afflict poor and predominantly rural people in developing nations. One significant disease that contributes to substantial morbidity in endemic areas is schistosomiasis, caused by infection with one of five species of blood fluke belonging to the trematode genus Schistosoma. Although there is one drug available for treatment of affected individuals in clinics, or for mass administration in endemic regions, there is a need for new therapies. A prominent target organ of schistosomes, either for drug or vaccine development, is the peculiar epithelial syncytium that forms the body wall (tegument) of this parasite. This dynamic layer is maintained and organized by concerted activity of a range of proteins, among which are the abundant tegumentary annexins. In this review, we will outline advances in structure-function analyses of these annexins, as a means to understanding tegument cell biology in host-parasite interaction and their potential exploitation as targets for anti-schistosomiasis therapies. LINKED ARTICLESThis article is part of a themed section on Annexins VII Programme. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-7 Abbreviations Anx, annexin; NTDs, neglected tropical diseases; RA, radiation attenuated; Sm, Schistosoma mansoni; TEMs, tetraspanin-enriched microdomains; TSP, tetraspanin Neglected tropical diseases (NTDs)NTDs include some 17 lesser known chronic infections that affect poor and disenfranchised people, primarily, but not exclusively, in developing nations (Hotez et al., 2007;Hotez and Fenwick, 2009). Chronic infections caused by NTDs lead to many adverse outcomes in affected populations and contribute substantially to human morbidity. In addition to microbial and protozoan diseases, NTDs include a number of helminth infections, such as diseases caused by flatworm parasites, notably schistosomiasis, echinococcosis and liver fluke diseases, as well as roundworm parasites, such as the major soil transmitted helminth infections (ascariasis, trichuriasis and hookworm diseases). Although no individual NTD rivals the major infectious threats of HIV, malaria or tuberculosis in terms of global impact of disease, collectively, the NTDs contribute substantially to morbidity throughout the world (Engels and Savioli, 2006). A number of factors present major challenges for the development of new treatments for NTDs. Firstly, NTDs are chronic diseases, which may reside in affected people as lifelong infections. Secondly, NTDs are not always associated with human mortality and the burden of these diseases can be subtle, hidden among such other measures of disease burden as hindered development, poor cognitive function and chronic ailments. Thirdly, as stated, NTDs often affect the poorest of the poor, people often unable to pay for medical treatments, especially for chronic illnesses. Hence, these diseases receive less attention than other, immediately lifethreatening infectious diseases. La...

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“…46 Another important schistosome antigen, Sm-14, a fatty acid binding protein has also been developed for clinical trials. 47,48 It is our belief that functionally important antigens will serve as appropriate targets for a schistosome vaccine. This is because schistosomes interact closely with their host, performing functions such as immune evasion, nutrient uptake and attachment.…”

Section: Vaccine Candidates and Search Of Functionally Important Vaccmentioning

confidence: 99%

Schistosomiasis vaccines

Siddiqui

Ganley-Leal

2011

Human Vaccines

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The biotechnology-value chain: Development of Sm14 as a schistosomiasis vaccine

Cited by 78 publications

References 15 publications

Fatty Acid- and Retinoid-binding Proteins Have Distinct Binding Pockets for the Two Types of Cargo

Fatty Acid- and Retinoid-binding Proteins Have Distinct Binding Pockets for the Two Types of Cargo

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

Schistosomiasis vaccines

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