Back to search

HAVBRUK2-Stort program for havbruksforskning

MucoProtect. Novel bio-mimicking nanocarriers for oral delivery of mucosal vaccines - protection at the first line of defence.

Awarded: NOK 8.0 mill.

Project Number:

280520

Application Type:

Project Period:

2018 - 2023

Location:

MucoProtect aims to develop a vaccine delivery system consisting of LPS alginate nanoparticles with properties tailored to meet the requirements of oral vaccines. The new delivery system ensures proper stimulation of the immune system in two ways: through the physical properties of the particle itself and through co-adjuvants (LPS) that will bind to and activate Toll-like receptors (TLR). LPS alginate particles will represent a new type of bio-mimicking vaccine carrier tailored for the purpose due to its biocompatibility, size, charge, encapsulation and adjuvant properties.

In parallel with the growth of aquaculture, infectious diseases have become an increasingly greater problem and currently represent the most significant constraint on sustainable aquaculture worldwide. For the salmon farming industry, the salmon lice challenge is currently the most important tasks to solve. One of the key areas of success in managing fish health in aquaculture has been the development of vaccines. However, for many diseases including salmon louse, vaccines are not available, and the farming industry keeps facing new challenges. Fish are continuously exposed to microorganisms in the aquatic environment. The mucosal surfaces lining the body form a physical barrier equipped with multiple dynamic and inducible immune effector mechanism crucial for the defence against environmental pathogens. Novel vaccine strategies that target these inductive sites properly are needed. Also, as antigens may not always evoke a sufficient immune response due to their nature, the path by which the vaccine is delivered and its auxiliary components are critical factors for the success of immunization. In MucoProtect, SINTEF and the Norwegian Veterinary Institute join advanced drug delivery technology with immune potentiating strategies to develop a novel and versatile vaccine delivery system customized for oral delivery of vaccines to fish: 1) New tailor-made and low-cost materials with inherent adjuvants will be developed and used to 2) produce nanoparticles specifically targeting key initiators of the immune response to prime the mucosal barriers to resist infection. If successful, MucoProtect will offer 3) new and more effective tools for preventing and controlling salmon lice that will increase the sustainability of the industry. MucoProtect will also 4) provide increased knowledge on central aspects of the mucosal immune system of Atlantic salmon and establish novel assays for assessing the effects of vaccines, both essential for future vaccine development. The main goal of MucoProtect-II will be to demonstrate that the new alginate particle-based delivery platform developed in MucoProtect-I can increase the efficacy of newly identified salmon lice antigen in Atlantic salmon. MucoProtect-II will have two dominant research questions: ? Can antigen in alginate particles, following (feed-based) oral administration, induce the production of antigen-specific antibodies in blood and mucus ? Can LPS via its immunogenicity act as immune stimulant in an oral particle-based vaccine, ie act as adjuvant? The project will use advanced equipment and methodology developed in MucoProtect-I to produce and characterize a range of alginate particles with variation in size, LPS content, (pH dependent) stability, antigen capacity and more. The project will develop new in vitro and ex vivo methods and models to test, among other things, stability of particles under different conditions, leakage of antigens and mucus penetration of particles of different sizes. The alginate particles will then be formulated for oral delivery (feed). Finally, the project will use vaccine trials as the critical yardstick for success: Can the antigen in the alginate particles induce specific antibodies after oral administration?

Activity:

HAVBRUK2-Stort program for havbruksforskning