New vaccine technologies for COVID-19 have been making headlines all around the world for obvious reasons. Among these newly developed vaccines are some based, not on introducing antigen into the host via the inoculum but, instead, on injecting host muscle with messenger RNA (mRNA) that codes for the production of virus specific immunogenic proteins.
Once in the muscle tissue, these mRNA sequences are able to instruct host cells around the site of the injection to start producing virus specific antigens which are then presented to the immune system in order to develop humoral and cell-mediated immune responses (refer Figure 1).
These vaccines cannot infect the host because they only contain nucleic acid sequences capable of instructing the synthesis of very specific viral proteins as opposed to a full genome required for replicating an organism. For over 15 years, Elanco have been trailblazing nucleic acid-based vaccine technologies for the prevention and control of viral disease affecting salmon production.
The result has been the launch of two DNA plasmid vaccines: the first was in 2005 for protection against Infectious Hematopoietic Necrosis (IHN) in North American production sites; and the second, Clynav™, was launched in 2017 to counter the serious disease threat posed by Pancreatic Disease (PD) in Norway, the UK and Ireland.
These two salmon vaccines contain a small circular DNA plasmid that is taken up by cells adjacent to the site of injection and directs production of the virus-specific antigens using the host cell machinery in a similar manner to the mRNA COVID-19 vaccines.
Improving PD control in Norwegian commercial sites
Clynav pioneered the way for the licensing of nucleic acid vaccines by the European Medicines Agency (EMA). This meant that during its development all trials for Clynav had to take place in land-based tanks in order to establish the safety of the technology before using in sea sites. Since 2017, Clynav’s performance in sea sites has been able to be monitored and its field efficacy established.
In response to this marked improvement in the control of PD, Britt Bang Jensen a senior researcher at the NVI stated ‘We have started a work to get more data to reveal what has actually happened this year. Understanding this is very important since PD has been a major burden on the fish and aquaculture industry for a long time. Among other things, we will look at the importance of different types of vaccine, including the Clynav vaccine from Elanco.’1 In Norway, Clynav has been used to protect millions of fish and hundreds of millions of doses have been sold in the process.
Recent trials comparing different PD vaccines
In three controlled field studies, the efficacy of commercially available PD vaccines was compared by measuring mortality and growth. A natural, clinical PD outbreak was confirmed with presence of both SAV 2 and SAV 3.
In these studies, only the group immunized with the DNA vaccine, Clynav, provided protection against mortality compared with the control group, this was significant in one of the studies2. Similarly, significant protection against PD-induced loss of growth was only found in the Clynav vaccinated group2.
Other advantages of DNA vaccines
Elanco’s DNA vaccines, including Clynav, have been successful not just because of their proven efficacy and duration of immunity but also for a number of specific additional advantages they offer (refer Table 1).
These vaccines are extremely safe because they: cannot cause infection (they don’t contain a micro-organism or the genome for a complete organism); don’t require an adjuvant (safer for the fish and the vaccinator); are administered via the intramuscular route (reducing the potential risk of organ damage); and are extremely stable, easy to store with a long shelf life.
Importantly, Clynav reduces the volume of oil adjuvants used. Oil adjuvants are associated with increased inappetence, resulting in loss of growth as well as the increased risk of adhesions and melanisation (dark spots) leading to downgrading of fillets at harvest. More recently, oil adjuvanted PD vaccines are among a number of factors that have been associated with the occurrence of cross-stitch spinal deformities in harvest sized salmon in Norway.3,4,5
For more information on Clynav and all Elanco Aqua products and services, please contact your Elanco representative.
Information call Elanco Animal Health on +44(0)1256 353131 or write to: Elanco UK AH Limited, First Floor, Form 2, Bartley Way, Bartley Wood Business Park, Hook RG27 9XA, United Kingdom
Use medicines responsibly www.noah.co.uk/responsible. Advice should be sought from the Medicine Prescriber. For further information consult the product SPC.
References: 1. Steep decline in the number of PD cases. October 8th, 2021 accessed at https://www.vetinst.no/nyheter/bratt-nedgang-i-antall-pd-tilfeller on 10.8.2021. 2. Magnus Vikan Røsæg et al. Effect of vaccines against pancreas disease in farmed Atlantic salmon. 2021. Journal of Fish Diseases; DOI: 10.1111/
jfd.13505. 3. Bæverfjord G., et al. ‘Cross-stitch’ vertebral deformities a new side effect of vaccination. 2021. Nofima Seminar ‘Fish biology challenges new technology’. Aqua Nor 2021: 24th August. Accessed https://vimeo.com/event/1226587/videos/591515167/ 4. Holm, H. A pathomorphological description of cross-stitch vertebrae in farmed Atlantic salmon (Salmo salar L.). 2020. Aquaculture: 526: 735382. 5. Thorarinsson, R., et al. Effect of a DNA and oil-adjuvanted vaccines for pancreas disease on spinal cross-stitch pathology development, growth and economic impact of commercially reared Atlantic salmon. 2020. ACFFA’s Aquaculture Research, Science and Technology Forum.
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