Cathepsin L1 mimotopes with adjuvant Quil A induces a Th1/Th2 immune response and confers significant protection against Fasciola hepatica infection in goats

Abstract

Thirty goats were randomly allocated in five groups of six animals each, for immunization with 1 × 10(14) phage particles of clones 11, 13, and 13 with Quil A adjuvant and wild-type M13KE phage at the beginning and 4 weeks later. The control group received phosphate-buffered saline. All groups were challenged with 200 metacercariae at week 6 and slaughtered 14 weeks later. The mean worm burdens after challenge were reduced by 46.91% and 79.53% in goats vaccinated with clones 13 and 13 with Quil A (P < 0.05), respectively; no effect was observed in animals immunized with clone 11 and M13KE phage. Animals receiving clones 11, 13, and 13 with Quil A showed a significant reduction in eggs output. Vaccinated animals produced parasite-specific total IgG antibody which were boosted after challenge with metacercariae of F. hepatica. Furthermore, levels of anti-phage total IgG increased rapidly within 2 weeks of the first vaccination and were always significantly higher in all vaccinated goats than in the infected control group. The fluke burden of goats immunized with clones 13 and 13 with Quil A was significantly correlated with IgG2 and total IgG. Goats vaccinated with phage clones produced significantly high titres of IgG1 and IgG2 antibodies indicating a mixed Th1/Th2 response. These data indicate that cathepsin L1 mimotopes has a potential as a vaccine candidate against Fasciola hepatica, whose efficacy will be evaluated in other host species, including those of veterinary importance.

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). …”

Fasciola and fasciolosis in ruminants in Europe: Identifying research needs

“…In vaccinated cattle, a Th1 response with high titres of IgG2 and low titres of IgG1 has been correlated with protection (Mulcahy et al., ). More recent trials in cattle (Golden et al., ), sheep (Maggioli et al., )and goats (Villa‐Mancera, Reynoso‐Palomar, Utrera‐Quintana, & Carreón‐Luna, ) found high levels of IgG2 and IgG1 associated with protection, possibly indicating a mixed Th1/Th2 response. As described in Section 7, Fasciola spp.…”

“…Using CL1/CL2 mimitopes, Villa‐Mancera et al. () reported 47% protection in sheep, and CL1 mimitopes on their own led to protection of 51% in sheep (Villa‐Mancera & Méndez‐Mendoza, ) and 46%–79% in goats (Villa‐Mancera et al., ). These promising results in sheep and goats have yet to be validated in subsequent trials and in field trials.…”

Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica-infected and/or vaccinated cattle and identification of protective linear B-cell epitopes

“…In the case of F. hepatica cathepsins, Harmsen et al (2004) described specific regions of FhCL1 and FhCL3 used to immunize rats which induced 40-64% fluke burden reduction [36]. Villa-Mancera (2008, 2011 and 2014) developed synthetic peptide mimotopes based on the FhCL1 protein sequence that could induce fluke burden reduction in sheep [37,38], mice [39] and goats [40]. In cattle, Cornelissen (1999) described peptides of FhCL1 that could be used as immunodiagnostics for F. hepatica infection [41].…”