Progress in PKD research
exploited therapeutically to combat the severity of PKD pathology. The fact that fi sh recovering from PKD acquire
protective immunity to re-infection paves the way towards the development of a PKD vaccine. Currently, PKD researchers are optimising the culture of the parasite in the laboratory, which is a crucial prerequisite in preparing large amounts of highly pure parasite material needed to devel- op whole-parasite vaccines. An alternative approach, widely used in the
discovery of protective antigens for vaccination, is to sequence the pathogen’s genes, which in turn enables researchers to characterise the full repertoire of proteins expressed by pathogens. Until recently, very little T. bryosalmonae se- quence data was available. Research at Aberdeen has led the way in developing T. bryosalmonae gene libraries, providing the impetus for subse- quent vaccine trials. Large numbers of parasite genes have now been sequenced, some of which encode for proteins known to be important as virulence or host-colonisation factors in other pathogen
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systems, or as molecules likely involved in specifi c developmental events in this parasite.
ies have been instru- mental in identi fying immune inhibitory molecules that could be exploited therapeuti - cally
“Our stud- ”
In taking the next steps towards PKD vaccine development, a BBSRC-funded project (to Dr Jason Holland and Prof Chris Secombes) was undertaken at Aberdeen using a DNA based approach to screen parasite gene pools by a technique called Expression Library Immunisation (ELI). DNA vaccination is still not widely used for veterinary products; never- theless, it represents a convenient, cost-effective, and powerful way to elicit protective immunity in fi sh. In this study T. bryosalmonae gene pools were tested for their ability to protect fi sh against advanced clinical disease and mortality.
Gene pools found to have a protective effect were fractionated further
and retested. After three rounds of ELI, a single protective gene pool was found. All parasite genes present in this pool have been fully characterised and a shortlist of candidate genes most likely to be causing the protective effect are currently being tested as single DNA vaccines. One of the major drawbacks in studying PKD has been the inability to purify intact parasites from infected kidney stages. Consequently, all of our vaccine studies so far have used purifi ed parasites from bryozoans. While most genes are likely to be similarly abundant in both hosts, some
may be dominant during the infection of fi sh. With the kidney and spleen being the focus of the fi sh-parasite interaction, from clinical disease to eventual parasite clearance, antigens that are dominant in these tissues may be at least partly responsible for the protective immunity that develops in
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