The effect of Quil A adjuvant on the course of experimental Fasciola hepatica infection in sheep.
ABSTRACT Fasciola hepatica infection causes significant clinical disease in ruminants. Current control methods, based on flukicidal drugs, are becoming less useful because of resistance in fluke populations. Vaccination would be a viable alternative, but as yet no vaccine to protect ruminants against liver fluke infection has been commercialised. Adjuvants can be used to enhance and promote protective immune responses by vaccines. In previous vaccination trials, we have observed a distinct adjuvant effect, or a degree of protection, in animals administered adjuvant alone in the absence of any specific F. hepatica antigen. Understanding this effect will be important for continuing efforts to develop vaccines effective against fasciolosis. This study investigated the effects of three adjuvants (Quil A, Freund's Incomplete and TiterMax Gold) on the course of experimental F. hepatica infection in 6-month-old sheep (n=33). At completion of the trial, all animals were necropsied to determine fluke burden and fluke weight. Quil A administration led to a significant reduction in faecal egg count (P<0.0001) and significantly higher parasite-specific serum antibody activity for all isotypes measured (P<0.01). This suggests that Quil A, which promotes a Th1 response, may be useful as an adjuvant in anti-Fasciola vaccines. Furthermore, it reinforces the results of our previous studies indicating that enhanced Th1 responsiveness to vaccine antigens is required to achieve protection against challenge by F. hepatica.
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ABSTRACT: Fasciola hepatica is a trematode helminth causing a damaging disease, fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our knowledge of the parasite's protein profile, and provide new insights into the development of more effective strategies to deal with fasciolosis. The objective of this study was to generate a comprehensive profile of F. hepatica proteins expressed during the chronic stage of infection in cattle by building on previous efforts in this area. The approach included an improved sample preparation procedure for surface and internal layers of the parasite, the application of nanoUPLC-ESI-qTOF-MS (nano ultra performance liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry) integrated with different acquisition methods, and in silico database search against various protein databases and a transcript database including a new assembly of publically available expressed sequence tags. Of a total of 776 identified proteins, 206 and 332 were specific to the surface and internal layers of the parasite, respectively. Furthermore, 238 proteins were common to both layers, with comparative differences of 172 proteins detected. Specific proteins not previously identified in F. hepatica, but shown to be immunomodulatory or potential drug targets for other parasites, are discussed.This article is protected by copyright. All rights reservedProteomics 04/2014; 14(12). · 3.97 Impact Factor
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ABSTRACT: The effects of two diets supplemented with flaxseed oil (FO) or vitamin E (VE) were studied in sheep infected with Fasciola hepatica. The control group (CO), not supplemented, had higher weight gain and faecal egg count (P<0.05) at the end of the study. At necropsy, the number (71.2 ±26.5) and size of flukes were lower in the FO group (P<0.01), probably due to the higher levels of white blood cells and lymphocytes (P<0.01). This group also had higher red blood cell and haematocrit values (P<0.01). The CO group had more severe hypoproteinaemia and hypoalbuminaemia, due to having the highest fluke burden (123.0 ±35.2), and also the highest IgG1 titre (P<0.01). The diet did not affect production or gene expression levels of IFN-γ and IL-4. On the other hand, the supplementation with VE led to a reduction in adult fluke burden (97.7 ±39.9) and lower lipid oxidation in the liver (P<0.001).Research in Veterinary Science 06/2014; · 1.51 Impact Factor
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ABSTRACT: The effects of the lipopolysaccharide (LPS) from Ochrobactrum intermedium in sheep with fasciolosis was reported previously, resulting in lower faecal egg counts and fluke burden. In the current study, we analyzed its immunological effects in two groups of sheep, treated (T) and controls (C). Fasciolosis induces a T helper (Th) type-2 response, characterized by IL-4 and IL-10 production; however, at the beginning of the infection, the IFN-γ production predominates (Th type-1 response). Although we did not find differences in IL-4 production or in the expression level of this gene in the hepatic lymph nodes, the expression level of IL-10 was higher (P<0.05) in the T group at 4 wpi. The IFN-γ production was higher (P<0.01) at 12 wpi as well as its level of expression at 4 wpi (P<0.05) in the T group. We found higher expression level of TGF-β at 4 wpi in the T group (P<0.05), associated with the previous report of thicker fibrous tracks in a treated group. Immunoglobulin G1, related with a Th type-2 response, was higher (P<0.01) in the T group at 4 and 12 wpi. In conclusion, the effects of LPS from O. intermedium could have resulted from a predominant Th type-2 immune response.Research in Veterinary Science 10/2014; · 1.51 Impact Factor