Periodic Reporting for period 1 - AntiVirFish (Antiviral Proteins Applied as Therapeutics in Aquaculture)
Période du rapport: 2022-05-01 au 2023-10-31
Aquaculture is the world’s fastest-growing animal production sector. The biggest global challenge to aquaculture production is infectious diseases that cause a 10 % loss of all cultured aquatic animals. Intensive fish farming augments diseases caused by bacteria, viruses, and parasites. However, few and not entirely effective vaccines are available for viral diseases in aquaculture, while there are no antiviral therapeutic treatments in unvaccinated fish. During a previous study, ERC-funded researchers identified antiviral proteins in rainbow trout nucleated red blood cells (RBCs) implicated in halting viral infections. The ERC-funded AntiVirFish project will perform a Proof of Concept of the identified antiviral molecules and assess the business opportunity.
In the last decades aquaculture seems to be the only real alternative for global fish food supply. At present, the aquaculture world production has reached 82.1 million tons worldwide representing the fastest growing animal production sector in the world. Among aquaculture species, salmonid aquaculture, trout and salmon species, are the highest-value species for global and European aquaculture. The biggest global constraint to aquaculture production is disease with an estimate of a 10% of all cultured aquatic animals lost because of infectious diseases, amounting to >10 billion USD in losses annually on a global scale. Among infectious diseases, viral outbreaks are a serious concern, since they are an impediment to the development, productivity, and profitability of fish farms. Intensive fish farming amplifies diseases caused by bacteria, viruses, and parasites, resulting in severe losses. Few vaccines are available for viral diseases in aquaculture and they are not completely effective. Moreover, up to date there are not antiviral therapeutic treatments to mitigate the outbreaks in unvaccinated fish or to diminish the percentage of losses do not covered by prophylactics vaccines. During my ERC Starting Grant our group identified a number of antiviral proteins in rainbow trout nucleated red blood cells (RBCs) implicated in halting viral infections. The objective of this project was to perform a Proof of Concept of the antiviral molecules previously identified. We have evaluated the new business opportunity of introducing a new antiviral therapeutic that decreases viral infection and related economic loss in aquaculture.
In the last decades aquaculture seems to be the only real alternative for global fish food supply. At present, the aquaculture world production has reached 82.1 million tons worldwide representing the fastest growing animal production sector in the world. Among aquaculture species, salmonid aquaculture, trout and salmon species, are the highest-value species for global and European aquaculture. The biggest global constraint to aquaculture production is disease with an estimate of a 10% of all cultured aquatic animals lost because of infectious diseases, amounting to >10 billion USD in losses annually on a global scale. Among infectious diseases, viral outbreaks are a serious concern, since they are an impediment to the development, productivity, and profitability of fish farms. Intensive fish farming amplifies diseases caused by bacteria, viruses, and parasites, resulting in severe losses. Few vaccines are available for viral diseases in aquaculture and they are not completely effective. Moreover, up to date there are not antiviral therapeutic treatments to mitigate the outbreaks in unvaccinated fish or to diminish the percentage of losses do not covered by prophylactics vaccines. During my ERC Starting Grant our group identified a number of antiviral proteins in rainbow trout nucleated red blood cells (RBCs) implicated in halting viral infections. The objective of this project was to perform a Proof of Concept of the antiviral molecules previously identified. We have evaluated the new business opportunity of introducing a new antiviral therapeutic that decreases viral infection and related economic loss in aquaculture.
In this project, we have been able to formulate an antiviral therapeutic based on mRNA of selected antiviral genes, encapsulated in lipid nanoparticles (LNPs), and administered with the feed. We first evaluated the protein expression efficiency after cell transfection with the selected mRNA, with or without LNPs, in vitro. Then, we evaluated the antiviral activity in cells transfected with the selected mRNA, in vitro. The antiviral activity was evaluated in vitro against four different viruses. Finally, the protein expression efficiency and antiviral activity of the mRNA-LNPs, administered in the feed, was evaluated in vivo, against three different viruses, being this the main achievement of the project. We have evaluated the commercial viability of the proposed antivirals and the roadmap for their development, following the applicable Regulations and Guidance for each phase of the development as indicated for Veterinary Medicinal Products.
We validated the efficacy of the antivirals based on mRNA-LNPs administered in the feed against three kind of viruses that affect salmonids aquaculture. The percentage of survival in fish fed with mRNAs-LNPs coding the protein of interest ranged from 10 to 30 %. The proposed antivirals would be the first salmonid antiviral reaching the market, and it would complement the prophylactic methods by a therapeutic action contributing to reduce the economic losses caused by viral outbreaks. Moreover, use of these antivirals would fit into the trend of eco-sustainable aquaculture supported by the policies of the main world organization, including the EC. All reasons make it worthwhile to continue supporting this project until the product can reach the market and, therefore, the end users.