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

Abstract

BackgroundSchistosomiasis 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.MethodsBALB/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.ResultsVaccination 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.ConclusionsHigher 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1500-y) contains supplementary material, which is available to authorized users.

Peptides Derived of Kunitz-Type Serine Protease Inhibitor as Potential Vaccine Against Experimental Schistosomiasis

“…The first injection contains AA0029 and Qs emulsified in Montanide, and the second injection, administered 5 days after the first, contains the antigen with AA0029 and Qs in the emulsion oil. Individual doses per injection in mice included 100 μg of AA0029, 20 μg of Qs, and 10 μg of either SmKT or SmKB in a final 100-μl volume of emulsion with Montanide based on our prior experience (54, 55). Mice were weighed and monitored for signs of anaphylactic shock, erythema at the injection site, and changes in behavior.…”

“…Mice were weighed and monitored for signs of anaphylactic shock, erythema at the injection site, and changes in behavior. Vaccinated and infection control mice were percutaneously challenged with 150 ± 8 S. mansoni cercariae by the ring method 2 weeks after the third vaccination (53–55). Mice were restrained with a mixture of 50 mg/kg ketamine (Imalgene1000, Merial), 5 mg/kg diazepam (Valium10, Roche Farma SA), and 1 mg/kg atropine (B. Braun, Madrid) administered intraperitoneally.…”

Metazoan Parasite Vaccines: Present Status and Future Prospects

“…For intestinal schistosomiasis, a recombinant S. mansoni 14 kDa monovalent fatty acid-binding protein (Sm14) (Moser et al, 1991 ; Tendler and Simpson, 2008 ; Coler et al, 2011 ), is currently in the final stages of phase II field trial testing in adult male subjects from endemic regions in Africa and Brazil (Supplementary Table 1 ) (Ricciardi and Ndao, 2015 ; Tendler et al, 2015 ; Santini-Oliveira et al, 2016 ). This antigen also shows promise as a dual-purpose helminthic vaccine against veterinary fasciolosis by conferring complete protection in mice challenged with Fasciola hepatica (67% for S. mansoni ) (Tendler et al, 1996 ) and vice versa with a similar native protein isolated from Fasciola hepatica (nFh12) that cross-protected mice against S. mansoni infection (>80% efficacy) (Vicente et al, 2016 ). This study is currently active and promising results could eventually lead to the first human antihelmintic vaccine.…”

Effect of Cytotoxic T-Lymphocyte Antigen-4 on the Efficacy of the Fatty Acid-Binding Protein Vaccine Against Schistosoma japonicum

“…Accordingly, previous studies have shown that the FABP, which absorbs, transports, and transforms fatty acids in host cell membranes (2), comprises a single effective vaccine against at least two parasites, Fasciola hepatica and S. mansoni (3). Furthermore, the FABP derived from F. hepatica has been reported to exert a strong protective effect against S. mansoni infection (4), and similarly, a recombinant S. mansoni FABP-pcDNAI plasmid was previously reported to elicit a high level of sm FABP-IgG antibody production, and to cause a strong (74.2%) decrease in the number of adult worms, as well as the number of eggs and granulomas (5). Moreover, the specific immune response elicited by, and tolerance of male volunteers (in non-schistosomiasis endemic areas) for a Sm FABP vaccine (formulated with a glucopyranosyl lipid A adjuvant, in an oil-in-water emulsion) has been successfully analyzed via landmark, open-knowledge phase-I and IIa clinical trials (6), and is currently being evaluated by phase-II/III trials (7).…”