Project: Improved vaccines against intracellular pathogens in aquaculture - combining PHARMAQ and Isconova technology

Emerging and persistent diseases caused by virus and intracellular bacteria are a great problem for the salmonid aquaculture industry with million Euro losses annually. There are vaccines on the market against many of these diseases, but the products are sub-optimal with regard to efficacy, resulting in mortality also in vaccinated fish. The current project aims to solve this problem by developing several novel vaccines with markedly increased efficacy. There is a significant market demand for such vaccines, as stated by two of the largest salmonid aquaculture companies in the world (User statements in the Annex). The new vaccines will also have a beneficial influence on fish health and welfare._x000D__x000D__x000D_The introduction of oil-based vaccines in the early 1990s has been a prerequisite for the growth and success of the salmonid aquaculture industry. At that time, extracellular bacterial diseases such as Furunculosis and Vibriosis caused serious problems resulting in extensive use of antibiotics. Within a few years after vaccination was implemented, the use of antibiotics dropped dramatically. Today the vaccines render full and long-lasting protection against the most common bacterial diseases such as Furunculosis and Vibriosis. In fact, every single fish in salmonid aquaculture in the CO markets Norway, UK/Ireland and Chile is currently vaccinated, demonstrating the importance of vaccination. _x000D__x000D_However, existing vaccines induce sub-optimal protection against viral diseases. Therefore, development of new, protective vaccines against the viral pathogens Infectious Pancreatic Necrosis Virus (IPNV) and Infectious Salmon Anemia Virus (ISAV) would make a substantial impact. Disease caused by IPNV and ISAV is a significant problem in Norway, UK/Ireland and Chile, even when fish are vaccinated. From mid-2007, an ISAV epidemic resulted in a total collapse of the aquaculture industry in Chile, clearly demonstrating the need for efficient vaccines against emerging viral diseases. Furthermore, disease caused by the intracellular bacteria Piscirickettsia salmonis (P.sal.) has been economically devastating for the Chilean aquaculture. The disease is now under better control due to vaccination, but the immunological protection is sub-optimal. Annually, infections caused by all these intracellular pathogens result in million Euro losses for the industry._x000D__x000D_The CO goal of the project is the development of improved vaccines against virus and intracellular bacteria causing disease in salmon. PHARMAQ (project leader) plans to launch several new products on the market based on the project results. As discussed above, the current vaccines on the market gives sub-optimal protection against intracellular pathogens. This is most likely due to the low capability of these vaccines to induce cell-mediated immunity (CMI), which is important for the efficient protection against intracellular pathogens (McCluskie MJ et al, pp 73-92 in Immunopotentiators in modern vaccines, Schijns V et al, 2006, Elsevier Academic Press). _x000D__x000D_In order to induce CMI, the approach is to further develop PHARMAQ`s vaccines to include an immune stimulatory adjuvant that will direct the responses towards CMI. An adjuvant is an excipient added in order to increase the product`s immunological effects and/or to induce a specific immunological response, for instance CMI. The Swedish company Isconova (participant) has developed a special adjuvant technology based on immune stimulatory complexes (ISCOM). Different saponin extracts from the cortex from Quillaja saponaria, together with phospholipids and cholesterol, forms matrix structures. These structures have proven to induce CMI and are now used in several veterinary vaccines against intracellular pathogens. The potential for use of this technology in vaccines for the aquaculture industry should be analogously big._x000D__x000D_In this project, PHARMAQ`s and Isconova`s complementary technologies will be combined in order to develop efficient vaccines against intracellular pathogens causing disease in salmonids. Isconova will be responsible for development and delivery of immune stimulatory adjuvants specifically designed for inducing CMI in salmon. In addition, Isconova will evaluate the type of immune response obtained by the different vaccine formulations. PHARMAQ is the project leader in the consortium, and is responsible for vaccine development and formulation, clinical trials and all marketing activities. _x000D__x000D_PHARMAQ and Isconova now have a unique opportunity to combine their technologies to develop and produce efficient novel vaccines for the expansive aquaculture industry.

Acronym	New-Vac (Reference Number: 5934)
Duration	01/01/2011 - 31/12/2013
Project Topic	The objective of the project is to develop improved vaccines against intracellular pathogens. PHARMAQ`s and Isconova`s technologies will be combined to achieve synergistic effects regarding vaccine efficacy and safety. Vaccine performance will be shown in relevant clinical challenge models.
Project Results (after finalisation)	Unfortunately, the CO conclusion from the project is that the immunstimulatory adjuvant Matrix F does not give any additive effect in multivalent injection vaccines for any of the antigen components studied in the project. Promising results were initially found for a Matrix F adjuvanted water based vaccine against IPN. However, the the long term protection induced by this vaccine was insufficient for a commercial product ._x000D__x000D_The CO positive result in the project was the successful development of a challenge model for IPNV injection vaccines. This model is now implemented in PHARMAQ in the development of new IPNV vaccines.
Network	Eurostars
Call	Eurostars Cut-Off 5

Project partner

Number	Name	Role	Country
2	Novavax AB	Partner	Sweden
2	PHARMAQ AS	Coordinator	Norway