Fasciola hepatica: Vaccination of rabbits with native and recombinant antigens related to fatty acid binding proteins

Muro, Antonio; Ramajo, V.; López, Julio; Simón, F.; Hillyer, George V.

doi:10.1016/s0304-4017(96)01131-4

Cited by 68 publications

(26 citation statements)

References 15 publications

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“…Proteolytic enzymes are important for digestion of the host tissue and are used in the parasite's defense mechanism. The proteolytic enzymes and antioxidants have been proposed as vaccine candidates against fascioliasis (5)(6)(7)(8)(9)(10)(11)(12)(13).…”

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confidence: 99%

Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

Figueroa-Santiago

Espino

2014

Infect Immun

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The liver fluke Fasciola hepatica is a highly evolved parasite that uses sophisticated mechanisms to evade the host immune response. The immunosuppressive capabilities of the parasite have been associated with antigens secreted through the parasite's tegument, called excretory-secretory products (ESPs). Proteomic studies have identified the fatty acid binding protein (FABP) as one of molecules present in the parasite ESPs. Although FABP has been investigated for potential use in the development of vaccines against fascioliasis, its direct interaction with cells of immune system has not been studied. In this study, FABP was purified in native form from soluble extracts of F. hepatica adult flukes using a combination of molecular sieving chromatography and preparative isoelectric focusing. The immunological effect of the purified protein, termed Fh12, was assayed in vitro using monocyte-derived macrophages (MDM) obtained from healthy human donors. Results from the assay indicate that Fh12 produced a significantly increased arginase expression and activity and induced the expression of chitinase-3-like protein (CHI3L1). The assay also showed that Fh12 downregulated the production of nitric oxide (NO) and the expression of nitric oxide synthase (NOS2). This indicates that Fh12 induced the production of alternatively activated macrophages (AAM). The results also demonstrated the ability of Fh12 to downregulate the secretion of the proinflammatory and inflammatory cytokines tumor necrosis factor alpha (TNF-␣), interleukin-12 (IL-12), and IL-1␤B, even after stimulation with lipopolysaccharide (LPS), as well as its ability to stimulate the overexpression of IL-10. These results suggest a potent anti-inflammatory role for Fh12, which could occur via targeting of Toll-like receptor 4 (TLR4).

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confidence: 99%

Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

Figueroa-Santiago

Espino

2014

Infect Immun

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“…[33] This protection level compares with other vaccine targets for fascioliasis with efficacies of 40-74%. [34][35][36] Moreover, sera from experimental mice infected with S. mansoni reacted to Fh-SLP-2 in vitro, thus showing crossreactivity [37] and suggesting that helminth SAPLIPs might be able to protect against trematodes more broadly. Interestingly, a number of human Sap domain-containing proteins, including granulysin, NK-lysin and surfactant protein B, have activity against a range of targets, such as tumor cells, bacteria, fungi and parasites, [38][39][40] and, accordingly, are considered components of the innate (not antibody provided) immune system.…”

Section: Proteins In Metabolic Pathways: Saposin-like Proteinsmentioning

confidence: 99%

“…[33] This protection level compares with other vaccine targets for fascioliasis with efficacies of 40-74%. [34][35][36] Moreover, sera 3…”

Section: Structures Of Parasite Proteinsmentioning

confidence: 99%

The Relevance of Structural Biology in Studying Molecules Involved in Parasite–Host Interactions: Potential for Designing New Interventions

et al. 2014

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1Mason et al. Structures of parasite proteinsNew interventions against infectious diseases require a detailed knowledge and understanding of pathogen-host interactions and pathogeneses at the molecular level. The combination of the considerable advances in systems biology research with methods to explore the structural biology of molecules is poised to provide new insights into these areas. Importantly, exploring threedimensional structures of proteins is central to understanding disease processes, and establishing structure-function relationships assists in identification and assessment of new drug and vaccine targets. Frequently, the molecular arsenal deployed by invading pathogens, and in particular parasites, reveals a common theme whereby families of proteins with conserved three-dimensional folds play crucial roles in infectious processes, but individual members of such families show high levels of specialisation which is often achieved through grafting particular structural features onto the shared overall fold. Accordingly, the applicability of predictive methodologies based on the primary structure of proteins or genome annotations is limited, particularly when thorough knowledge of molecular level mechanisms is required. Such instances exemplify the need for experimental threedimensional structures provided by protein crystallography, which remain an essential component of this area of research. In the present article, we review two examples of key protein families recently investigated in our laboratories, which could represent intervention targets in the metabolome or secretome of parasites. IntroductionInfectious diseases caused by eukaryotic pathogens represent a major disease burden to humans world-wide. In the absence of effective preventative approaches and new intervention strategies, this burden is likely to increase further, [1,2] compounded by food and water shortages, economic crises, wars and climate change, particularly in disadvantaged countries. In addition, there is evidence of increasing problems with resistance in pathogens against a broad range of chemotherapeutic agents, compromising the treatment of infectious diseases. [3] Moreover, in spite of major efforts, there are very few examples of success in developing new drugs and vaccines against eukaryotic pathogens, [4,5] indicating that alternative methods are needed at a time of major advances in molecular and computer technologies. In our opinion, the development of new treatments requires a detailed understanding of pathogens, host interactions and the molecular processes of disease. For instance, knowledge of the three-dimensional structures of proteins with pivotal roles in disease, and the probing of their underlying biology are crucial for understanding the pathogenesis. Through establishing the relevant structure-function relationships, one can elucidate how individual proteins function, so that new ways of disrupting relevant pathways can be found, in order to facilitate the identification of new drug and vaccine targets. ...

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“…Experimental infection of rabbits with F. gigantica Six rabbits were infected orally with viable F. gigantica encysted metacercariae, 30 metacercariae for each (Muro et al 1997). Blood samples were taken from ear vein at 2 weeks intervals starting 15 days post infection until 60 days.…”

Section: Determination Of Antigens Protein Contentmentioning

confidence: 99%

Significance of a common 65 kDa antigen in the experimental fasciolosis and toxoplasmosis

Shaapan

Toaleb²,

Abdel-Rahman³

2013

J Parasit Dis

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In the current study, cross-reaction between two important zoonotic parasites; extracellular helminthes Fasciola gigantica and intracellular protozoa Toxoplasma gondii was proved by enzyme linked immunosorbent assay. Five antigens were used to identify and compare the cross-binding activities in the prepared antisera. Two F. gigantica antigens; adult flukes (FgA) and eggs (FgEA) were used to detect IgG in T. gondii naturally infected human sera (TgIHS) and experimentally infected sera of sheep (TgISS), mice (TgIMS) and rats (TgIRS). Three types of T. gondii antigens; RH (TgRHA), local sheep isolate (TgLA) and ME49 isolate (TgMEA) were used to detect cross binding activities in F. gigantica experimental infected rabbit sera (FgIRS) and F. gigantica naturally infected bovine sera (FgIBS). The cross-binding activities in the prepared antisera were strongly directed towards FgA and TgLA rather than the other antigens. The characterization of the five antigens using SDS-PAGE showed 4 common bands of FgA and TgLA; 165, 97, 76, and 65 kDa. While two common bands were observed between TgRHA, TgMEA and FgA; 165, and 65 kDa. Whereas, two common bands found between three types of T. gondii antigens and FgEA were identified; 165 and 65 kDa. The immunogenic cross-reactive bands between FgA and TgLA with F. gigantica infected bovine sera were identified by immunoblot. In FgA, the common immunogenic bands were 165, 65 and 14 kDa. While in TgLA, common immunogenic bands were 165 and 65 kDa. Whereas, the common immunogenic band between FgA and TgLA identified with T. gondii experimentally infected sheep sera was 65 kDa. The current research proves cross reaction between F. gigantica and T. gondii. One common band of 65 kDa showed broad immunogenic cross-reactivity with the developed antisera raising the prospect of being putative common immunodiagnostic candidate of both infections.

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Fasciola hepatica: Vaccination of rabbits with native and recombinant antigens related to fatty acid binding proteins

Cited by 68 publications

References 15 publications

Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

Fasciola hepatica Fatty Acid Binding Protein Induces the Alternative Activation of Human Macrophages

The Relevance of Structural Biology in Studying Molecules Involved in Parasite–Host Interactions: Potential for Designing New Interventions

Significance of a common 65 kDa antigen in the experimental fasciolosis and toxoplasmosis

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