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Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems.

Vicente B, López-Abán J, Rojas-Caraballo J, del Olmo E, Fernández-Soto P, Muro A - Parasit Vectors (2016)

Bottom Line: In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%).Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15.Native FABP is more effective than both recombinant systems.

View Article: PubMed Central - PubMed

Affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007, Salamanca, Spain.

ABSTRACT

Background: Schistosomiasis is a water-borne disease afflicting over 261 million people in many areas of the developing countries with high morbidity and mortality. The control relies mainly on treatment with praziquantel. Fatty acid binding proteins (FABP) have demonstrated high levels of immune-protection against trematode infections. This study reports the immunoprotection induced by cross-reacting Fasciola hepatica FABP, native (nFh12) and recombinantly expressed using two different expression systems Escherichia coli (rFh15) and baculovirus (rFh15b) against Schistosoma mansoni infection.

Methods: BALB/c mice were vaccinated with native nFh12 or recombinant rFh15 and rFh15 FABP from F. hepatica formulated in adjuvant adaptation (ADAD) system with natural or chemical synthesised immunomodulators (PAL and AA0029) and then challenged with 150 cercariae of S. mansoni. Parasite burden, hepatic lesions and antibody response were studied in vaccination trials. Furthermore differences between rFh15 and rFh15b immunological responses (cytokine production, splenocyte population and antibody levels) were studied.

Results: Vaccination with nFh12 induced significant reductions in worm burden (83%), eggs in tissues (82-92%) and hepatic lesions (85%) compared to infected controls using PAL. Vaccination with rFh15 showed lower total worm burden (56-64%), eggs in the liver (21-61%), eggs in the gut (30-77%) and hepatic damage (67-69%) using PAL and AA0029 as immunomodulators. In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%). We observed a significant rise in TNFα, IL-6, IL-2, IL-4 and high antibody response (IgG, IgG1, IgG2a, IgM and IgE) in mice immunised with either rFh15 or rFh15b. Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15.

Conclusions: Higher level of protection is obtained by using Fasciola hepatica-derived FABP protein against Schistosoma mansoni infection. Native FABP is more effective than both recombinant systems. It could be due to post-translational modifications or FABP isoform or changes in the recombinant proteins.

No MeSH data available.


Related in: MedlinePlus

Representative hepatic lesion area reduction in BALB/c mice after vaccination. Natural and recombinant FABP (nFh12, rFh15 or rFh15b) formulated with the adjuvant adaptation (ADAD) vaccination system were used with the natural immunomodulator PAL or the synthetic AA0029 and challenged with 150 cercariae of S. mansoni in three separate experiments
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Fig2: Representative hepatic lesion area reduction in BALB/c mice after vaccination. Natural and recombinant FABP (nFh12, rFh15 or rFh15b) formulated with the adjuvant adaptation (ADAD) vaccination system were used with the natural immunomodulator PAL or the synthetic AA0029 and challenged with 150 cercariae of S. mansoni in three separate experiments

Mentions: Significant reductions in recovered total worms (83 %), males (87 %) and females (82 %) were observed in BALB/c mice immunised with nFh12 formulated in ADAD with the natural immunomodulator PAL (PAL+Qs+nFh12) compared to the infected control group (Table 1). Also, a significant decrease in the number of eggs present in the liver (82 %) and in the intestine (92 %) were detected (Table 1). In concordance, hepatic damage extension was significantly reduced (85 %) compared to the infection control group (Table 1, Fig. 2). Furthermore, mice injected only with PAL+Qs did not show significant protection in terms of parasite burden or hepatic lesions (Table 1). A significantly higher production of specific anti-nFh12 IgG was observed in the nFh12 vaccinated group compared to uninfected, infected or adjuvant controls after the second immunisation which remained until the end of the experiment (Fig. 3a and Additional file 1: Table S1). Also all infected groups showed a significant production of IgG, IgG1 8 weeks post-infection against SoSmAWA but only vaccinated with PAL+Qs+nFh12 showed significant IgG2a production (Fig. 4a and Additional file 2: Table S2).Table 1


Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems.

Vicente B, López-Abán J, Rojas-Caraballo J, del Olmo E, Fernández-Soto P, Muro A - Parasit Vectors (2016)

Representative hepatic lesion area reduction in BALB/c mice after vaccination. Natural and recombinant FABP (nFh12, rFh15 or rFh15b) formulated with the adjuvant adaptation (ADAD) vaccination system were used with the natural immunomodulator PAL or the synthetic AA0029 and challenged with 150 cercariae of S. mansoni in three separate experiments
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836169&req=5

Fig2: Representative hepatic lesion area reduction in BALB/c mice after vaccination. Natural and recombinant FABP (nFh12, rFh15 or rFh15b) formulated with the adjuvant adaptation (ADAD) vaccination system were used with the natural immunomodulator PAL or the synthetic AA0029 and challenged with 150 cercariae of S. mansoni in three separate experiments
Mentions: Significant reductions in recovered total worms (83 %), males (87 %) and females (82 %) were observed in BALB/c mice immunised with nFh12 formulated in ADAD with the natural immunomodulator PAL (PAL+Qs+nFh12) compared to the infected control group (Table 1). Also, a significant decrease in the number of eggs present in the liver (82 %) and in the intestine (92 %) were detected (Table 1). In concordance, hepatic damage extension was significantly reduced (85 %) compared to the infection control group (Table 1, Fig. 2). Furthermore, mice injected only with PAL+Qs did not show significant protection in terms of parasite burden or hepatic lesions (Table 1). A significantly higher production of specific anti-nFh12 IgG was observed in the nFh12 vaccinated group compared to uninfected, infected or adjuvant controls after the second immunisation which remained until the end of the experiment (Fig. 3a and Additional file 1: Table S1). Also all infected groups showed a significant production of IgG, IgG1 8 weeks post-infection against SoSmAWA but only vaccinated with PAL+Qs+nFh12 showed significant IgG2a production (Fig. 4a and Additional file 2: Table S2).Table 1

Bottom Line: In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%).Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15.Native FABP is more effective than both recombinant systems.

View Article: PubMed Central - PubMed

Affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007, Salamanca, Spain.

ABSTRACT

Background: Schistosomiasis is a water-borne disease afflicting over 261 million people in many areas of the developing countries with high morbidity and mortality. The control relies mainly on treatment with praziquantel. Fatty acid binding proteins (FABP) have demonstrated high levels of immune-protection against trematode infections. This study reports the immunoprotection induced by cross-reacting Fasciola hepatica FABP, native (nFh12) and recombinantly expressed using two different expression systems Escherichia coli (rFh15) and baculovirus (rFh15b) against Schistosoma mansoni infection.

Methods: BALB/c mice were vaccinated with native nFh12 or recombinant rFh15 and rFh15 FABP from F. hepatica formulated in adjuvant adaptation (ADAD) system with natural or chemical synthesised immunomodulators (PAL and AA0029) and then challenged with 150 cercariae of S. mansoni. Parasite burden, hepatic lesions and antibody response were studied in vaccination trials. Furthermore differences between rFh15 and rFh15b immunological responses (cytokine production, splenocyte population and antibody levels) were studied.

Results: Vaccination with nFh12 induced significant reductions in worm burden (83%), eggs in tissues (82-92%) and hepatic lesions (85%) compared to infected controls using PAL. Vaccination with rFh15 showed lower total worm burden (56-64%), eggs in the liver (21-61%), eggs in the gut (30-77%) and hepatic damage (67-69%) using PAL and AA0029 as immunomodulators. In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%). We observed a significant rise in TNFα, IL-6, IL-2, IL-4 and high antibody response (IgG, IgG1, IgG2a, IgM and IgE) in mice immunised with either rFh15 or rFh15b. Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15.

Conclusions: Higher level of protection is obtained by using Fasciola hepatica-derived FABP protein against Schistosoma mansoni infection. Native FABP is more effective than both recombinant systems. It could be due to post-translational modifications or FABP isoform or changes in the recombinant proteins.

No MeSH data available.


Related in: MedlinePlus