mRNA vaccines for fast responses to fish emergent infectious diseases in a context of global climate change – FishRNATherm

Environmental changes linked to global warming imposes new challenges on aquaculture, in particular through emerging infectious diseases. Fast production of effective vaccines, particularly against viruses, is therefore essential for sustainable aquaculture, in order to prevent infectious diseases that pose a major threat to its development and to the aquatic ecosystems connected to fish farms. As fish are ectotherms, the effectiveness of their adaptive immune response varies with the temperature of the environment, impacting both their ability to control infections and the protection provided by vaccination. The impact of climate change on the effectiveness of their vaccination is therefore potentially considerable, and there is an urgent need to understand the mechanisms involved, so that we can adapt the design of vaccines and adjuvants to new changing environmental conditions. mRNA vaccines offer interesting advantages in this respect: they can be developed rapidly, are a priori safer than DNA vaccines, and are formulated in nanoparticles whose rapid progress promises effective administration via the mucosal route. During two previous ANR projects, we developed an mRNA vaccine formulated in liponanoparticles (LNP), offering virtually complete protection of rainbow trout against Viral Hemorrhagic Septicemia (VHS). We propose here to build a solid conceptual framework for the rapid development of mRNA vaccines against emerging infectious diseases in farmed fish. We will characterize the influence of temperature on the development of the immune response induced by the anti-SHV mRNA vaccine. We will also adapt the lipid composition of the mRNA vehicle (LNP), and optimize micellar adjuvants, to vaccinate effectively at different temperatures.