Demonstration of a high level of cross reactivity between different strains of salmonid alphavirus: results from experimental and field studies.


22 October 2013

Dr David Graham and Dr Marian McLoughlin 

Salmon Pancreas Disease  Virus  (SPDV), also referred to as  Salmonid  alphavirus (SAV),  causes pancreas disease (PD) in Atlantic salmon and sleeping disease in rainbow trout. While all strains of the virus are recognised to be closely related members of the same virus species, they can be assigned to six genogroups (SAV subtypes 1 ‐6), based on minor differences in the sequences of their nucleic acid. The geographical distribution of these subtypes in marine salmon production is now well characterized. In Ireland, SAV isolates of subtypes 1 and 4 are present (plus the only isolate of SAV subtype 6 made to date). In Scotland, isolates of subtypes 1, 2, 4 and 5 are present, while in Norway SAV subtype 3 has been the predominant strain, although subtype 2 isolates have emerged recently. Within each of these countries there is also evidence of further geographic localisation of different subtypes. 

While the minor differences between these subtypes at the genetic level is well recognised, the serological cross reactivity between the genetically distinguishable strains of SAV has not been systematically  characterized  until  recently.  In  addition  to  providing  further  insights  into  the relationship  between  strains,  these  differences  also  have  practical  relevance  in  terms  of  the efficacy of vaccines and the selection of antibodies for diagnostic testing. 

A  recent  study  conducted  by  the  Fish  Diseases  Unit  (FDU)  of  the  Agri‐food  and  Biosciences Institute in Belfast and MSD Animal Health (Bergen) has investigated these relationships through cross‐neutralisation studies using sera from both experimental and field studies. 

In the first part of the work, serum samples from groups of fish which had each been challenged under experimental conditions with a single subtype of virus were used. The neutralising ability of these sera, as measured against the virus used to generate them (homologous virus‐serum pairs) was  then  compared  with  the  titres  obtained  when  they  were  tested  in  turn  against  strains representing each of the 5 other subtypes (heterologous virus‐serum pairs).  

The second part of the study conducted a similar analysis, using serum samples from natural outbreaks of PD in farmed salmon. These had been shown to have been caused by SAV subtypes 1, 4 and 5, based on diagnostic investigations (including virus strain typing) carried out previously by the Fish Diseases Unit.  

With the exception of the level of SAV subtype 6 neutralization by heterologous sera, good cross neutralisation was detected between strains representing all other subtypes using  sera  from experimental infections, albeit with some variation in the titres recorded. A similar pattern was evident with field sera, except that heterologous neutralisation of the SAV6 strain was more evident. These findings are consistent with those of earlier, more limited studies, with a high level of serological cross reactivity between isolates representing all subtypes typically being detected. 

The vaccine NORVAX Compact PD contains a SPDV strain that genotypically clusters as a SAV1 strain. While other elements of the immune system have also been shown to be capable of contributing  to  a  protective  immune  response  the  data  suggest  that  an  immune  response generated against SAV subtype 1 can be expected to provide protection against challenge with the major other subtypes currently encountered in aquaculture. This is in line with another report showing that a SAV1‐based vaccine protects at least as well as a vaccine based on a SAV3 isolate when fish are challenge with an SAV3 strain. 

Compared to its use in other diagnostic arenas, VN testing is still not widely used in aquaculture, although it is becoming more widely accepted. From a diagnostic perspective, it is critical that the SAV subtype used as a test virus is susceptible to neutralization by antisera raised against all strains of the virus. The results of the current study suggest that this is the case for all of the major subtypes, with testing therefore expected to demonstrate a high level of diagnostic sensitivity, 
particularly when applied at cage or site level. 
 
D A Graham, H R Rowley and P Frost (2013) Cross‐neutralization studies with salmonid alphavirus subtype 1–6 strains: results with sera from experimental studies and natural infections. Journal of Fish Diseases DOI: 10.1111/jfd.12167 
For more information about NORVAX COMPACT PD, go to http://aqua.merck‐animal‐health.com, e‐mail aqua@merck.com or contact your local MSD Animal Health representative. 
REF: 088STREP 

About Merck Animal Health 
Today's Merck is a global healthcare leader working to help the world be well. Merck Animal Health (known as MSD Animal Health outside the United States and Canada), is the global animal health business unit of Merck. 
Merck Animal Health offers veterinarians, farmers, pet owners and governments one of the widest ranges of veterinary pharmaceuticals, vaccines and health management solutions and services. Merck Animal Health is dedicated to preserving and improving the health, well‐being and performance of animals. It invests extensively in dynamic and comprehensive R&D resources and a modern, global supply chain. Merck Animal Health is present in more than 50 countries, while its products are available in some 150 markets. For more information, visit www.merck‐animal‐health.com. 
 
Legal Notes 
NORVAX is a trademark of Intervet International B.V. or affiliated companies or licensors and is protected by copyrights, trademark and other intellectual property laws. Copyright © 2012 Intervet International B.V., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved. This press release contains information on veterinary products based on international registration dossiers and may refer to products that are either not available in your country or are marketed under a different trade name. In addition, the approved indications as well as safety and efficacy data for a specific product may be different depending on local regulations and approvals. For more information, read the product labeling that applies to your country or contact your local Merck/MSD Animal Health representative.

REFERENCE 082CPD