Company Statement

Clarification to article: “Novel vaccine technologies impact human and salmon health outcomes” (Fish Farmer Yearbook, 2022).

Regarding the article published in the 2022 edition of the Fish Farmer Yearbook entitled ‘Novel vaccine technologies impact human and salmon health outcomes’, and in response to a complaint, Elanco would like to clarify the following points:

1. In describing the advantages of DNA vaccines over conventional vaccines it was implied that DNA vaccines hold an advantage regarding the plasmid stability and hence a longer product shelf life facilitating ease of storage and shipping. As approximately 50% of the approved PD vaccines in the UK for use in Atlantic Salmon offer two years of shelf life, the same shelf life as CLYNAV ™ , we acknowledge that our statement cannot be applied generally.

2. The statement “…These vaccines are extremely safe because they: cannot cause infection (they don’t contain a micro-organism or the genome for a complete organism)…” could, if taken out of context, imply that conventional PD vaccines in the market are less safe. This statement is correct with regard to the mode of action of live attenuated vaccines. These vaccines require the infection of the host in order to generate a protective immune response. It is generally accepted that attenuated vaccines produce transient side effects sometimes even consistent with the pathology they are intended to prevent1,2. It should be made clear that all current conventional PD vaccines used within the UK market are based on inactivated viral vaccine technology. All medicines, including vaccines, which have a Marketing Authorization in the UK have undergone rigorous risk benefit evaluation and are deemed to be safe and effective.

The use of DNA plasmid vaccine technology does, however, offer distinct advantages when compared with a conventional oil adjuvated inactivated viral PD vaccine. The development of technology which precludes the use of mineral oil has significant impacts on the reduction of risk for the fish3,4. The use of mineral oil adjuvants in ‘traditional’ vaccines can lead to variable degrees of side effects in the form of melanisation and adhesions5. In order to qualify this point, reference is made to Table 1., which states the adverse reactions registered in the UK approved SPC* for both CLYNAV ™ and ALPHA JECT ® micro 1 PD. Oil-adjuvanted vaccines have been mentioned in the recently reported ‘cross-stitch’ pathology identified in Norway6.

As previously mentioned, the use of oil-adjuvated vaccines can cause variable levels of adhesions and melanisation in the peritoneal cavity5. These side effects are well documented5,7,8,9,10. The fact that CLYNAV ™ is administered by intramuscular injection in the area immediately anterior and lateral to the dorsal fin, in the epaxial muscle, and does not contain a mineral oil adjuvant mitigates against these documented reactions11. Getting things wrong when vaccinating via the intraperitoneal route using oil-adjuvated vaccines can negatively affect fish welfare, growth, and result in costly downgrades at harvest due to the described side effects of melanisation, adhesions, and spinal deformity.

CLYNAV ™ : A new era in vaccine technology Novel vaccine mode of action

CLYNAV ™ ’ s DNA plasmid instructs cells adjacent to the site of injection to produce specific antigens of interest for salmon alpha virus (SAV) which can then be presented to the immune system. CLYNAV ™ ’ s DNA plasmid is taken up by the cells adjacent to the site of injection and directs production of the antigens using the host cell machinery. These antigens are recognized as foreign proteins and are then processed and displayed on the cell surface triggering a broad, potent immune response including both antibody (humoral) and cell-mediated components. Figure 2 illustrates how CLYNAV ™ uses the myocytes and the antigen presenting cells (APC) to trigger the cell-mediated (CD8* T cells with MHC I) and humoral immunity pathways (CD4* T cells with MHC II), respectively. 4,13

Proven high performance PD control

A study was conducted independently, measuring the efficacy of PD vaccines in commercially reared Atlantic salmon, using mortality and growth as the key outcome variables. This study was conducted on commercial farming sites where the presence of either, or both, SAV2 and SAV3 subtypes were detected. 14

The below vaccine groups were assessed: The cumulative mortality until harvest for the salmon vaccinated with CLYNAV ™ was the lowest (2.9%) compared to an overall cumulative mortality of 4.2% for all the groups combined. The cumulative mortality for the group vaccinated with ALPHA JECT ® micro 1PD was 3.7%. 14 The CLYNAV ™ vaccinated group also had higher slaughter weights at harvest than all the other groups including fish vaccinated with ALPHA JECT ® micro 1PD. In fact the CLYNAV ™ vaccinated fish were 0.67kg heavier than those vaccinated with ALPHA JECT ® micro 1PD (refer Figure 3). 14