Strategic plan
This proposal is part of FRDC Industry Development Program, Strategy - Aquaculture development - production and production systems. However, it also has strong capacity building elements, including training of at least one PhD student in the area of fish health/immunology and providing workshops for industry and researchers (Use of immunostimulants in finfish culture, Immune response in fish). It provides leadership development by having a full time young researcher (CI - Dr Richard Morrison) working on this project. Thus, this proposal will significantly contribute to Human Capital Development Program, Leadership and Vocational Development. Improved knowledge of immune response and immunomodulators was identified as one of the key research areas for aquatic animal health in Research and Development Plan Aquatic Animal Health Subprogram. Priorities covered by this key research area included immunology in aquatic vertebrates (nature of disease and host-pathogen interactions), immunomodulators (aquatic animal health management) and development of tools for immune status monitoring as a means of implementing health management strategies (surveillance and monitoring). All three elements are included in this proposal. This proposal is consistent with R&D plans for Atlantic Salmon Aquaculture Subprogram and with Aquafin CRC AGD research program. It also addresses targeted priority: fish health, within Program 2: Industry Development, Key R&D issues for fisheries and aquaculture in SA, South Australia's Fisheries and Aquaculutre Research and Development Strategy 2002-2007. The research focus is within Tasmanian Fisheries and Aquaculture, Aquaculture Strategic Research Plan 1999-2004. This proposal fits well into Aquafin CRC strategy and mission by significant contribution of its outcomes to achieving sustainable aquaculture in Australia through reduction of economic impact of diseases in farmed fish, development of environmentally friendly approaches to disease management and training aquaculture industry and researchers in the fields of fish immunology.
Need for research
It is impossible to prevent the presence of pathogens in aquaculture systems, particularly in sea-cage grow-out. Most disease outbreaks occur when there is an interaction between pathogens and susceptible fish (for example immunocompromised fish due to stress). This will result in lowering the performance of the fish and possibly mortalities. Sustainable aquaculture of finfish requires lowering the risk of disease outbreaks and replacing disease treatment with control strategies. The use of immunomodulators is essential to achieve these goals, in particular in times of increased disease risk or reduced immunocompetence. Our understanding of host-pathogen interactions and immune response allows for the use of appropriate immunomodulators. For example, if a disease is caused by overreaction of the inflammatory response, traditional immunostimulants will not improve the outcomes. Similarly, there is a need to determine correct timing and dose for immunomodulation in mariculture. Improved immune response would improve fish performance during grow-out.
Importantly immunomodulators are natural products that are derived from microbes, thus avoiding the use of chemical products. Commerical immunomodulators have been successfully used in aquaculture worldwide however only experimentally in Australia. For example oral immunomodulators MicroVital significantly increases survival rates of Atlantic salmon following Vibrosis challenge and 32% gain in survival rates of salmon fed natural immunomodulators (ß glucans and nucleotides) following exposure to IPN (exotic viral disease) challenge has been achieved in trials in Norway. However, there is little information available for fish species other than salmon or diseases other than commercially important in Northern Hemisphere. There is a need to develop immunomodulation strategies that are directly applicable to Australian mariculture, either specific for our species or diseases affecting Australian aquaculture industry (for example Amoebic Gill Disease) or unique conditions such as water temperatures.
Benefits
For Atlantic salmon we will address AGD management by investigation of immunomodulators. AGD is the main health problem for salmon industry and successful use of immunomodulation could provide an answer, particularly in combination with other management strategies.
This project is generic and the benefits are not limited to the species we will use as a model in our investigation. Other finfish aquaculture industries will also benefit from training and workshops provided by this project.
Final report
Before this project our knowledge of immune response in Amoebic Gill Disease (AGD) was fundamentally limited and more information was required to assess the potential for immunomodulators in the management of AGD.
We confirmed that injection of bacterial DNA motif (CpG oligonucleotides) six days before AGD challenge can offer signficant protection to Atlantic salmon (relative percent survival up to 52.5%). However, there was no effect if the fish were challenged immediately post injection with bacterial DNA. This suggests that while there is a potential benefit from the use of immunostimulants, their application is limited because their efficacy is directly linked to the timing of an outbreak, which can be unpredictable in the field. While fish which survived an initial AGD episode show increased resistance to subsequent AGD infection, in contrast to some diseases this effect cannot be simply explained by the presence of antibodies. The duration of exposure (or number of exposures) appears to be important for the development of serum antibodies. Mucus antibodies could not be detected in Atlantic salmon that survived AGD challenge. Microarray experiments and further gene expression studies suggested that there is a loss of cell-cycle control in AGD lesions. Furthermore, immune pathways are affected since the down-stream effect(s) of the initial inflammatory signals were not detectable. It is possible that this significantly contributes to the extremely high rate of mortality in unmitigated AGD epizootics.
While we have achieved our objectives and answered many of the original questions, new issues have emerged from our research. These include a lack of understanding of the mechanisms of inhibition of inflammatory and immune pathways, significance of antibody response (if any) in AGD, and the potential for vaccine antigen discovery through the use of anti-peptide antibody. The presence and role of a more localised antibody response in the gill mucus or epithelium (currently undetectable) warrants further investigation.
In conclusion, we now have a better understanding of AGD pathogenesis and the reasons why the host immune response is ineffective in this disease. In particular, we have shown that immune pathways are inhibited in Atlantic salmon affected by AGD.
Keywords: Amoebic Gill Disease, salmon, aquaculture, immunostimulants, inflamation, gene expression, transcriptome analysis.
