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Establishing new concepts and approaches for future vaccine development against parasitic pathogens of cattle

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New vaccine developed to combat liver flukes

Fasciolosis is a disease of ruminants caused by liver flukes (Fasciola hepatica), which also infects millions of people around the world. An EU-funded initiative has been established to develop a vaccine to combat this threat to human health and livestock.

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Liver flukes are one of nature’s most successful parasites as they have the greatest global distribution and the widest range of hosts of all helminths (commonly known as parasitic worms). The ability of F. hepatica to flourish is related to the efficiency by which it invades its host (most usually sheep and cattle) and suppresses their protective immune responses. Thus the goal of the FLUKVAC (Establishing new concepts and approaches for future vaccine development against parasitic pathogens of cattle) project was to develop a successful vaccination against liver fluke by blocking the ability of helminth parasites to suppress the immune system of its host. The use of chemicals to treat worms is not effective in the long term because of the continual emergence of drug-resistant parasites. Furthermore, the presence of chemical and antibiotic residues in food has heightened consumers concerns about how food is produced and what they are eating. Vaccines, on the other hand leave no chemical residues in food, are environmentally friendly and are acceptable to both users and consumers. Development of effective new vaccines against early fasciolosis requires an understanding of how the parasite infects the ruminant host, induces tissue damage and modulates the host immune response particularly in the first days of infection. Studies have shown that as the parasite migrates through the intestinal epithelium clinical signs are not evident, although an immunological response is induced, as illustrated by the large number of immune cells infiltrating into the peritoneal cavity. Since the parasite migrates from the intestine to the liver via the peritoneum FLUKVAC investigated the peritoneal fluid of infected animals. This has provided new information of the early immune response, which can be exploited for vaccine development. The data can also be used to identify host-specific proteins that may act as biomarkers of infection. Proteomic analysis of the peritoneal fluid from infected and non-infected sheep identified 324 proteins, with 31 proteins uniquely observed in the infected animals. Components of the liver extracellular matrix, including collagen, periostin and the vascular cell adhesion molecule 1 (VCAM-1) exhibited increased expression associated with early fasciolosis. This may be important in signalling host immune responses to tissue damage. FLUKVAC has therefore successfully characterised major biomarkers of parasite induced liver damage such as periostin and VCAM-1, which may be used for diagnosis and for vaccine development in order to reduce or prevent liver pathology.

Keywords

Fasciolosis, Fasciola hepatica, FLUKVAC, periostin, VCAM-1

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