Vaccine potential of recombinant saposin-like protein 2 against Fasciolosis gigantica in mice

Kueakhai, Pornanan; Changklungmoa, Narin; Riengrojpitak, Suda; Chaichanasak, Pannigan; Meemon, Krai; Chaithirayanon, Kulathida; Chantree, Pathanin; Sansri, Veerawat; Itagaki, Tadashi; Sobhon, Prasert

doi:10.1016/j.vaccine.2013.09.027

Cited by 22 publications

(13 citation statements)

References 29 publications

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“…These results are consistent with earlier studies performed with other F. hepatica antigens (Kesik et al, 2007; Wedrychowicz et al, 2007) and antigens from other parasitic organisms (Dempster et al, 1996; Malgorzata, 2004), which have also demonstrated that inclusion bodies constitute a stable and effective vehicle of antigen delivery with poor differences in immunogenicity compared to the purified antigens. However, the protection induced by FhSAP2-IBs in mice was lower than those observed in the same animal species (74.6–78.5%) with the homolog protein of F. gigantica (FgSAP2) administered subcutaneously in FA (Kueakhai et al, 2013) and lower than those previously reported for the rabbit model of fascioliasis using TiterMax (Espino and Hillyer, 2004) or FA (Espino and Rivera, 2010). These observations confirm the notion that the vaccine potential of FhSAP2 is highly depending of the animal species and the experimental conditions.…”

Section: Discussionmentioning

confidence: 58%

“…In contrast, in the FhSAP2-IBs vaccinated animals enhanced levels of both IgG1 and IgG2a antibodies were detected, implicating mixed Th1/Th2 antibody response associated to the protection. Although is not clear the role of antibodies in the protection against F. hepatica this type of mixed humoral response has been reported by other vaccination studies in both F. hepatica and F. gigantica (Chantree et al, 2013; Golden et al, 2010; Kueakhai et al, 2013; Preyavichyapugdee et al, 2008). Moreover, the observation that FhSAP2-IBs vaccinated animals developed significantly higher levels of IgG2a, companied with high levels of serum IFNγ and TNFα, and significantly lower levels of IL-4 than controls support the hypothesis that the Th1-response could be necessary to induce protection against fascioliasis, which has been also suggested by other authors (Hacariz et al, 2009).…”

Section: Discussionmentioning

confidence: 72%

“…Over the last decade a large number of native and recombinant parasite proteins have been identified and tested as vaccine in a number of animals models. Some of these molecules includes leucinaminopeptidase (Maggioli et al, 2011a), cathepsin-L (Chantree et al, 2013; Golden et al, 2010; Piacenza et al, 1999), thioredoxin-glutathion reductase (Maggioli et al, 2011b), glutathione S-transferase (Sexton et al, 1990; Sexton et al, 1994), fatty acid binding protein (Casanueva et al, 2001; Martinez-Fernandez et al, 2004) and saposin-like protein-2 (Espino et al, 2010; Kueakhai et al, 2013). All these vaccine candidates have induced partial levels of protection that range between 46.9–83% in different animal models, which indicates that a vaccine against F. hepatica is not a chimera but an attainable goal.…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Rivera

Espino

2016

Experimental Parasitology

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Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund’s adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide™ ISA720. Animals received three injections containing 20μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0–62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Rivera

Espino

2016

Experimental Parasitology

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“…With regard to F. gigantica , MoAbs have been produced against total extract (Fagbemi et al 1997), against ES antigens (Estuningsih et al 2004, 2009; Demerdash et al 2011), against partially purified native proteins derived from tegument (Chaithirayanon et al 2002; Krailas et al 2002; Anuracpreeda et al 2006, 2009 b ) and against recombinant proteins such as FABPs (Sirisriro et al 2002; Allam et al 2012), a SAPLIP member from F. gigantica (FgSAP2) (Kueakhai et al 2013 a , b ) and cathepsin B3 protease (Anuracpreeda et al 2013).…”

Section: Diagnosis With Stool Samplesmentioning

confidence: 99%

Diagnosis of human fascioliasis by stool and blood techniques: update for the present global scenario

2014

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Before the 1990s, human fascioliasis diagnosis focused on individual patients in hospitals or health centres. Case reports were mainly from developed countries and usually concerned isolated human infection in animal endemic areas. From the mid-1990s onwards, due to the progressive description of human endemic areas and human infection reports in developing countries, but also new knowledge on clinical manifestations and pathology, new situations, hitherto neglected, entered in the global scenario. Human fascioliasis has proved to be pronouncedly more heterogeneous than previously thought, including different transmission patterns and epidemiological situations. Stool and blood techniques, the main tools for diagnosis in humans, have been improved for both patient and survey diagnosis. Present availabilities for human diagnosis are reviewed focusing on advantages and weaknesses, sample management, egg differentiation, qualitative and quantitative diagnosis, antibody and antigen detection, post-treatment monitoring and post-control surveillance. Main conclusions refer to the pronounced difficulties of diagnosing fascioliasis in humans given the different infection phases and parasite migration capacities, clinical heterogeneity, immunological complexity, different epidemiological situations and transmission patterns, the lack of a diagnostic technique covering all needs and situations, and the advisability for a combined use of different techniques, at least including a stool technique and a blood technique.

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“…The other classes were represented by one EC each, and included Fructose-bisphosphatase (FBPase; 3.1.3.11), a key enzyme in gluconeogenesis that has not been identified as a target in helminths; 3′,5′-cyclic-nucleotide phosphodiesterase (PDE; 3.1.4.17), inhibitors for which have been suggested to be good potential drugs for targeting parasitic nematodes due to their ability to disrupt the C . elegans life cycle and nematode-specific active binding sites 35 ; and Leucyl aminopeptidase (LAP-1/cathepsin III; 3.4.11.1), a potential drug target in Leishmania 32 , known to be an excretory/secretory (ES) product and a modulator of host immune system 36 , and previously studied as a potential vaccine candidate for the liver fluke, Fasciola hepatica 37,38 .…”

Section: Resultsmentioning

confidence: 99%

Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics

Tyagi

Elfawal

Wildman

et al. 2019

Sci Rep

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Targeting chokepoint enzymes in metabolic pathways has led to new drugs for cancers, autoimmune disorders and infectious diseases. This is also a cornerstone approach for discovery and development of anthelmintics against nematode and flatworm parasites. Here, we performed omics-driven knowledge-based identification of chokepoint enzymes as anthelmintic targets. We prioritized 10 of 186 phylogenetically conserved chokepoint enzymes and undertook a target class repurposing approach to test and identify new small molecules with broad spectrum anthelmintic activity. First, we identified and tested 94 commercially available compounds using an in vitro phenotypic assay, and discovered 11 hits that inhibited nematode motility. Based on these findings, we performed chemogenomic screening and tested 32 additional compounds, identifying 6 more active hits. Overall, 6 intestinal (single-species), 5 potential pan-intestinal (whipworm and hookworm) and 6 pan-Phylum Nematoda (intestinal and filarial species) small molecule inhibitors were identified, including multiple azoles, Tadalafil and Torin-1. The active hit compounds targeted three different target classes in humans, which are involved in various pathways, including carbohydrate, amino acid and nucleotide metabolism. Last, using representative inhibitors from each target class, we demonstrated in vivo efficacy characterized by negative effects on parasite fecundity in hamsters infected with hookworms.

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Vaccine potential of recombinant saposin-like protein 2 against Fasciolosis gigantica in mice

Cited by 22 publications

References 29 publications

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Diagnosis of human fascioliasis by stool and blood techniques: update for the present global scenario

Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics

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