Development of a mucosally-delivered and active salmon louse vaccine for Atlantic salmon aquaculture

The salmon louse, Lepeophtheirus salmonis, is an ectoparasite that feeds on the mucus, skin, underlying tissues, and blood of salmonid fish and is a particular issue for farmed Atlantic salmon. The economic impact of salmon lice on the global Atlantic salmon industry is estimated to be $1 US billion annually. The Atlantic salmon aquaculture industry is a key contributor to the UK economy, worth over £1 billion annually. The Scottish Government intends to double the value of Atlantic salmon production between 2016 and 2030. However, salmon lice are the biggest constraint to the expansion of the industry. The industry uses various methods to control salmon lice infestations, including chemotherapeutants, thermo or hydro-licers, snorkel cages and cleaner fish. However, there are major challenges with the application and efficacy of these approaches, and the salmon farming industry continues to look for new environmentally friendly solutions to control salmon lice infections, which offer better fish welfare, less handling, less stress, and less physical trauma than the methods currently employed. A commercial salmon louse vaccine would provide a practical, safe, and eco-friendly approach to managing salmon lice and enhance the current strategies used to control salmon lice. No commercial vaccines are available for L. salmonis; developing an efficacious vaccine against this parasite has been challenging. Traditional methods for administering salmon lice vaccines by intraperitoneal injection have shown limited success, primarily due to their inability to elicit a suitable immune response at the site where the lice feed - i.e., the mucosal surface of the skin. This project focuses on developing an effective prototype vaccine to protect Atlantic salmon from salmon lice by stimulating a protective mucosal immune response within their skin. We aim to create a vaccine that can be orally administered to fish to enhance both systemic and mucosal immune responses, thus increasing the chances of generating effective mucosal immune protection against sea lice. Appropriate vaccine targets are those that affect parasite biology, such as attachment, development and/or maturation and which are present during parasitic stages of the louse's life cycle. Our innovative approach will use reverse vaccinology (RV) to quickly identify key biological targets within the salmon louse for novel vaccine development. This involves identifying antigens in silico from the genome of the salmon louse using bioinformatic tools. We will integrate this with an artificial intelligence (AI) antigen prediction platform (EpitopePredikt) to assist in antigen discovery and docking potential, pinpointing immunogenic epitopes that can be recognised by fish immunoglobulins (IgM and IgT antibodies). This will allow a targeted selection of vaccine candidates for assessment in vivo. These will be integrated into a unique mucosal antigen-presenting scaffold for oral delivery. Multiple antigens will be expressed on a single scaffold using an epitope/peptide expression platform (EpitoGen), so fewer fish are needed for antigen assessment in immunisation/infection trials, and the immune response of fish is exposed to several recombinant epitopes on the scaffold to produce a more robust immune response. The efficacy of our vaccine will be measured by its ability to reduce the number of lice (and/or the fecundity of female salmon lice) on vaccinated fish that have been experimentally infected with salmon lice. This project is an interdisciplinary collaboration between the Moredun Research Institute (MRI), the University of Stirling's Institute of Aquaculture (IoA), Bimeda Animal Health (BAH), and Vertebrate Antibodies Ltd (VAL) with an Industrial Award Partnership contribution from BAH.

Traditional methods for administering salmon lice vaccines by intraperitoneal injection have shown limited success, primarily due to their inability to elicit a suitable immune response at the site where the lice feed - i.e., the mucosal surface of the skin. We aim to create a vaccine that can be orally administered to fish to enhance both systemic and mucosal immune responses, thus increasing the chances of generating effective mucosal immune protection against sea lice. Appropriate vaccine targets are those that affect parasite biology, such as attachment, development and/or maturation and which are present during parasitic stages of the louse's life cycle. Our innovative approach will use reverse vaccinology (RV) to quickly identify key biological targets within the salmon louse for novel vaccine development. This involves identifying antigens in silico from the genome of the salmon louse using bioinformatic tools. We will integrate this with an artificial intelligence (AI) antigen prediction platform (EpitopePredikt) to assist in antigen discovery and docking potential, pinpointing immunogenic epitopes that can be recognised by fish immunoglobulins (IgM and IgT antibodies). This will allow a targeted selection of vaccine candidates for assessment in vivo. These will be integrated into a unique mucosal antigen-presenting scaffold for oral delivery. Multiple antigens will be expressed on a single scaffold using an epitope/peptide expression platform (EpitoGen), so fewer fish are needed for antigen assessment in immunisation/infection trials, and the immune response of fish is exposed to several recombinant epitopes on the scaffold to produce a more robust immune response. The efficacy of our vaccine will be measured by its ability to reduce the number of lice (and/or the fecundity of female salmon lice) on vaccinated fish that have been experimentally infected with salmon lice.