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

开发用于大西洋鲑鱼水产养殖的粘膜递送活性鲑鱼虱疫苗

• 批准号: BB/Y006534/1
• 负责人: Kimberly Thompson
• 金额: $ 161.82万
• 依托单位: Moredun Research Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY006534%2F1
• 关键词: Development; mucosally; delivered; active; salmon

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.

鲑鱼虱，黄铁虫鲑鱼，是一种以粘液，皮肤，潜在的组织和鲑鱼鱼的血为食的，是养殖大西洋鲑鱼的一个特殊问题。鲑鱼虱子对全球大西洋鲑鱼产业的经济影响估计为每年10亿美元。大西洋鲑鱼水产养殖业是英国经济的关键因素，每年价值超过10亿英镑。苏格兰政府打算在2016年至2030年之间的大西洋鲑鱼产量价值两倍。但是，鲑鱼虱是该行业扩张的最大限制。该行业使用各种方法来控制鲑鱼虱子的侵扰，包括化学疗法，热疗法或水力固定器，浮潜笼子和清洁的鱼。但是，这些方法的应用和效率面临着重大挑战，鲑鱼农业行业继续寻找新的环保解决方案来控制鲑鱼许可感染，这些解决方案比当前使用的方法提供了更好的鱼类福利，更少的处理，更少的压力和更少的身体创伤。商业鲑鱼损失疫苗将提供一种实用，安全和环保的方法来管理鲑鱼许可并增强目前用于控制鲑鱼许可证的策略。鲑鱼没有商业疫苗；针对这种寄生虫开发有效的疫苗一直具有挑战性。传统的通过腹膜内注射给鲑鱼虱子疫苗的方法显示出有限的成功，这主要是由于它们无法在虱子进食的部位引起合适的免疫响应 - 即皮肤的粘膜表面。该项目着重于开发有效的原型疫苗，以通过刺激皮肤中受保护的粘膜免疫响应来保护大西洋鲑鱼免受鲑鱼虱子的影响。我们旨在创建一种可以口服的疫苗，以增强全身性和粘膜免疫调味剂，从而增加产生有效的粘膜免疫保护对海虱保护的机会。适当的疫苗靶标是影响寄生虫生物学的疫苗，例如依恋，发育和/或成熟，并且在损失生命周期的寄生阶段存在。我们的创新方法将使用反疫苗学（RV）快速识别鲑鱼虱中的关键生物学靶标，以进行新的疫苗开发。这涉及使用生物信息学工具从鲑鱼损失的基因组中鉴定抗原。我们将将其与人工智能（AI）抗原预测平台（Epitopepredikt）相结合，以协助抗原发现和停靠潜力，从而确定可以通过鱼类免疫球蛋白（IgM和IgM和IgT抗体）识别的免疫原性表位。这将允许在体内进行有针对性的候选疫苗候选物。这些多种抗原将使用表位/肽表达平台（表皮）在单个支架上表达，因此在免疫化/感染试验中，抗原评估所需的鱼类需要较少，并且鱼类的免疫响应暴露于几种重组表现效果上，以产生更强大的免疫反应。我们的疫苗的效率将通过减少经过实验感染鲑鱼许可的疫苗的鱼类的许可证数量（和/或女性鲑鱼许可证的繁殖力）来衡量。该项目是Moredun研究所（MRI），斯特林大学水产养殖研究所（IOA），Bimeda Animal Health（BAH）和脊椎动物抗体有限公司（Val）与BAH的工业奖励合伙贡献之间的跨学科合作。