Immunoprophylaxis AgainstFasciola hepaticain Rabbits Using a Recombinant Fh15 Fatty Acid-Binding Protein

Abstract

Previous studies of ours have demonstrated that a recombinant protein (Fh15) related to fatty acid-binding proteins did not induce significant protection in rabbits challenged 2 or 4 wk postimmunization over nonimmunized controls. In the current study, rabbits were immunized with Fh15 and challenged with Fasciola hepatica metacercariae 12 and 20 wk later. In the current study in which longer lag periods for challenge infection after the second immunization were used, worm burden reductions compared to adjuvant controls were a significant 43% and 76%, respectively. Importantly, rabbits immunized with Fh15 had significant numbers of immature flukes, 66% in the 12-wk period and 84% in the 20-wk lag period as compared to controls. In addition, liver lesions were clearly diminished in the vaccinated rabbits. Enzyme-linked immunosorbent assay absorbance values showed that immunized rabbits developed high antibody levels to Fh15 from 8 wk after the first immunization and did not increase after challenge. These results suggest that a recombinant F. hepatica molecule related to fatty acid-binding proteins induces protective (worm burden reductions), anti-fecundity (immature flukes), and anti-pathology (less liver lesions) effects in rabbits and may serve as a model for the immunoprophylaxis of fascioliasis.

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

“…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 .…”

“…Therefore, they use carriers to uptake such lipids directly from the host and transport them to specific destinations within parasite, a process in which FABP could play an important role. Thus, a major reason for interest in trematode FABPs relies in their potential role in drug delivery 3 and the fact that Fasciola hepatica and Schistosoma mansoni FABPs may be cross-protective antigens 4–7 .…”

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

“…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). …”

“…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.…”

Native and Recombinant Fatty Acid Binding Protein 3 fromFasciola Hepaticaas a Potential Antigen

“…Fatty acid binding proteins are widely distributed, low molecular weight, highly expressed cytosolic proteins that are capable of binding, in noncovalent manner, a broad range of lipophilic ligands (1,22). It has been defined that the recombinant Fh15 (FABP1) from F. hepatica has immunoprophylactic properties -decreasing of adult forms number and limiting their pathological effect (5). Recombinant Sm14 (from Schistosoma mansoni) has been also used as a vaccine and has showed high activity against cercaria (16,21).…”