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Blocking BAFF signaling to treat Proliferative Kidney Disease (PKD) in trout

Project description

Application of recombinant protein technology for treatment of kidney disease in trout

Proliferative kidney disease (PKD) in salmonids is caused by the myxozoan parasite Tetracapsuloides bryosalmonae leading to high mortality. The EU-funded PKDControl project’s goal is to validate the application of recombinant protein to reduce the damage inflicted by the parasite. The study capitalises on the preliminary observation that the cytokine B cell activating factor (BAFF) mediates the dysregulation of kidney B cell subsets during PKD. The intramuscular injection of a plasmid coding for the extracellular domain of BAFF receptor (tBAFF-R) led to BAFF signalling blocking, indicating the potential of this approach for reducing the mortality of the infected stocks. The project’s objective is to produce recombinant tBAFF-R in yeast and evaluate its bioactivity in laboratory and field tests.

Objective

PKDControl is aimed at validating the use of a recombinant protein to reduce the pathology and mortality produced by proliferative kidney disease (PKD) in salmonids. PKD is caused by the myxozoan parasite Tetracapsuloides bryosalmonae that affects both cultured and wild salmonids in North America and Europe. It can eventually lead to mortalities of up to 90%, generating great economic loses every year to the aquaculture industry. This problem may be aggravated by global warming since the incidence and severity of PKD are exacerbated by rising temperatures.
During my ERC Consolidator Grant we have demonstrated that the cytokine BAFF (B cell activating factor) mediates the dysregulation of diverse B cell subsets present in the kidney during PKD. We have shown that the intramuscular injection of a plasmid coding for the extracellular domain of BAFF receptor (BAFF-R) led to secretion of this truncated BAFF-R (tBAFF-R) that, in turn sequestered circulating BAFF, blocking BAFF signalling. Preliminary field tests in Spain and USA demonstrated the potential of this approach in reducing the pathology and mortality of the infected stocks. In this project, we will recombinantly produce tBAFF-R in yeast to facilitate its uptake by the industry and test its bioactivity in both lab and field experiments. In parallel to these technical activities, we will reinforce the IPR position (based on a PCT - international - patent application that has received a very positive patentability report by the patent office). We will also design a long-term IPR strategy and develop a knowledge transfer strategy through the recently initiated collaboration with a fish health management company, willing to reach commercialization of tBAFF-R under a license and to contribute with their own funds to the activities carried out under this project. A business case will also be elaborated to support the commercialization of the recombinant tBAFF-R to ensure that the innovation potential of our results.

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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 135 000,00
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost
No data

Beneficiaries (2)