Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD

López‐Abán, Julio; Casanueva, Patricia; Nogal, Juan José; Arias, M.; Morrondo, P.; Díez‐Baños, P.; Hillyer, George V.; Martínez-Fernández, A. R.; Muro, Antonio

doi:10.1016/j.vetpar.2006.12.017

Cited by 38 publications

(17 citation statements)

References 27 publications

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“…Both, Fh12 and Fh15 proteins have been extensively used to induce protection to challenge with F . hepatica infection in mice, sheep 5, 38 or rabbits 4 . Moreover, some studies have used Fh12 or Fh15 proteins to induce cross-protection against Schistosoma mansoni or S .…”

Section: Discussionmentioning

confidence: 99%

Recombinant Fasciola hepatica fatty acid binding protein suppresses toll-like receptor stimulation in response to multiple bacterial ligands

Ramos‐Benitez

Ruiz-Jiménez

Aguayo

et al. 2017

Sci Rep

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Recently, we reported that a native Fasciola hepatica fatty acid binding protein (FABP) termed Fh12 is a powerful anti-inflammatory protein capable of suppressing the LPS-induced expression of inflammatory markers in vivo and in vitro. Because the purification of a protein in native form is, in many situations not cost-beneficial and unsuitable for industrial grade scale-up, this study accomplished the task of optimizing the expression and purification of a recombinant form of FABP (Fh15). Additionally, we ascertained whether this molecule could exhibit a similar suppressive effect on TLR-stimulation and inflammatory cytokine expression from macrophages than those previously demonstrated for the native molecule. Results demonstrated that Fh15 suppresses the expression of IL-1β and TNFα in murine macrophages and THP1 Blue CD14 cells. Additionally, Fh15 suppress the LPS-induced TLR4 stimulation. This effect was not impaired by a thermal denaturing process or blocked by the presence of anti-Fh12 antibodies. Fh15 also suppressed the stimulation of various TLRs in response to whole bacteria extracts, suggesting that Fh15 could have a broad spectrum of action. These results support the possibility of using Fh15 as an excellent alternative for an anti-inflammatory drug in preclinical studies in the near future.

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Section: Discussionmentioning

confidence: 99%

Recombinant Fasciola hepatica fatty acid binding protein suppresses toll-like receptor stimulation in response to multiple bacterial ligands

Ramos‐Benitez

Ruiz-Jiménez

Aguayo

et al. 2017

Sci Rep

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“…These observations confirm the notion that the vaccine potential of FhSAP2 is highly depending of the animal species and the experimental conditions. Trials on a number of vaccine candidates, glutathione S-transferase (Morrison et al, 1996; Sexton et al, 1990; Sexton et al, 1994), cathepsin L- proteases (Mulcahy et al, 1999; Villa-Mancera et al, 2014) and fatty acid binding proteins (Casanueva et al, 2001; Lopez-Aban et al, 2007; Martinez-Fernandez et al, 2004) have also shown a lack of consistency in the degree of protection obtained, which may be due, in part, to differences in the experimental design, for example route of immunization (injection or oral), form of antigen, presence of adjuvants in the vaccine and differences in the animal models (van Milligen et al, 2000; Vercruysse et al, 2004; Wedrychowicz et al, 2003). …”

Section: Discussionmentioning

confidence: 99%

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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“…These proteins can potentially prevent oxidative damage to trematode cellular components by binding fatty acids and ions involved in oxidative stress (23, 24). Previous studies have shown that vaccines containing FABPs induce partial immune protection in experimentally infected mice and sheep (25, 26). Moreover, F. hepatica FABPs also appear to be important molecules for inducing cross-immunity against Schistosoma species (27).…”

Section: Introductionmentioning

confidence: 99%

Fasciola hepaticaFatty Acid Binding Protein Inhibits TLR4 Activation and Suppresses the Inflammatory Cytokines Induced by Lipopolysaccharide In Vitro and In Vivo

Martin

Cabán-Hernández

Figueroa-Santiago

et al. 2015

The Journal of Immunology

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Toll-like receptor 4 (TLR4), the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial lipopolysaccharide (LPS), which is a major cause of the high mortality associated with bacterial sepsis. We report here that a single intraperitoneal injection of 15μg Fasciola hepatica fatty acid binding protein (Fh12) 1 hour before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are good source of IL12p70 and TNFα, and critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow derived macrophages (bmMΦs). Whereas Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL12, TNFα, IL6 and IL1β cytokines as well as iNOS2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR-ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 co-receptor. Moreover, it suppresses phosphorylation of ERK, p38 and JNK. The potent anti-inflammatory properties of Fh12 demonstrated here open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

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Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD

Cited by 38 publications

References 27 publications

Recombinant Fasciola hepatica fatty acid binding protein suppresses toll-like receptor stimulation in response to multiple bacterial ligands

Recombinant Fasciola hepatica fatty acid binding protein suppresses toll-like receptor stimulation in response to multiple bacterial ligands

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

Fasciola hepaticaFatty Acid Binding Protein Inhibits TLR4 Activation and Suppresses the Inflammatory Cytokines Induced by Lipopolysaccharide In Vitro and In Vivo

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