Location: Cool and Cold Water Aquaculture ResearchTitle: Sequencing and characterization of a novel micro exon gene (Tb-MEG1) in a myxozoan parasite: its utility as a vaccine candidate and as a biomarker of proliferative kidney disease (PKD) in rainbow trout
|FARBER, MARC - University Of Aberdeen|
|TAFALLA, C - Centro De Investigación En Sanidad Animal (CISA-INIA)|
|Wiens, Gregory - Greg|
|OKAMUR, B - Natural History Museum - London|
|HARTIKAINEN, H - Eawag - Swiss Federal Institute Of Aquatic Science And Technology|
|WANG, T - University Of Aberdeen|
|HOLLAND, J - University Of Aberdeen|
|SECOMBES, C - University Of Aberdeen|
Submitted to: UK & International Veterinary Vaccinology Network Conference
Publication Type: Abstract Only
Publication Acceptance Date: 11/15/2018
Publication Date: 1/10/2019
Citation: Farber, M., Tafalla, C., Wiens, G.D., Okamur, B., Hartikainen, H., Wang, T., Holland, J., Secombes, C.J. 2019. Sequencing and characterization of a novel micro exon gene (Tb-MEG1) in a myxozoan parasite: its utility as a vaccine candidate and as a biomarker of proliferative kidney disease (PKD) in rainbow trout. UK & International Veterinary Vaccinology Network Conference. Paper No. D2T37.
Technical Abstract: PKD is one of the most serious diseases affecting trout aquaculture in the UK. Caused by the myxozoan parasite, Tetracapsuloides bryosalmonae, PKD is elicited by the temperature-dependent development of parasite spore sacs in colonial bryozoans. Our investigations have focused on putative T. bryosalmonae virulence factors in order to unravel host immune evasion mechanisms exploited by the parasite, whilst shortlisting candidates for vaccine studies. Recently we uncovered an unknown gene which appears to exhibit a mechanism of antigenic variability previously thought to be unique to helminth parasites, particularly in schistosomes parasites. These so called micro-exon genes (MEGs) are intrinsically disordered secreted proteins some of which have been shown to interfere with host immunity. Over 75% of the coding region of MEGs consists of micro exons (<36 bp) which drive antigenic variability through alternative splicing. Splice variants are thought to enable greater plasticity in host protein targets to subvert immunity over the course of infection. Here we report the sequencing and characterization of the first non-helminth MEG gene from different T. bryosalmonae populations. The 264 amino acid open reading frame of the full length molecule is encoded by 65 exons, with only 5 exons > 30 bp. The protein is predicted to consist of an intrinsically disordered loop containing a tandem repeat region flanked by a conserved signal peptide at the N-terminus and a C-terminal domain with a strongly predicted nuclear localization signal. Using a validated anti-MEG MoAb, we have demonstrated the protein is endogenously expressed in and on the surface of parasites and a subset of host immune cells within the kidneys of infected fish. We have also demonstrated a potent Tb-MEG1-specific IgM antibody response in sera from parasite-infected farmed rainbow in three different countries. In addition, this antigen has been tested in combination with other antigens in vaccine trials and was shown to partially reduce the gross kidney pathology associated with PKD. Overall, the discovery and characterisation of Tb-MEG1 may provide insights into host immune evasion mechanisms exploited by myxozoan parasites whilst having major implications concerning the evolution of antigenic variability in metazoan parasites.