1. Field of Invention
The disclosure relates generally to the fields of immunology and fish production.
2. Related Art
Infectious pancreatic necrosis virus is the causative agent of infectious pancreatic necrosis disease (IPN) that infects salmonids and remains a serious problem in the aquaculture industry (1). IPN is especially contagious and destructive to juvenile trout and salmon. Highly virulent strains may cause greater than 70% mortality in hatchery stocks over a period of two months (21). This disease is especially destructive in salmonid eggs and fingerlings (25). Survivors of infection can remain lifelong asymptomatic carriers and serve as reservoirs of infection, shedding virus in their feces and reproductive products. Losses due to IPNV on salmon smoltification have been estimated at 5% (16). Economic losses due to IPNV in aquaculture were estimated to be over $60 million in 1996 (4), (17). This has been reduced as vaccines for salmonids became available based on killed virus or recombinantly produced viral peptides (13, 17). However, these vaccines are not completely effective and can only be used in fairly large fish due to the reliance on injection for vaccination.
IPNV is a double-stranded RNA virus of the Birnaviridae family (5) and is the type species of the Aquabirnavirus genus (6). Birnaviruses have a non-enveloped, single-shelled particle structure comprised of a single protein capsid layer with T=13 icosahedral symmetry (2). All birnavirus genomes have two dsRNA segments. The IPNV genome's two dsRNA segments are designated segments A and B. Segment B (2777 nucleotides) encodes a minor internal polypeptide VP1 (94 kDa), which is the virion-associated RNA-dependent RNA polymerase (RdRp) (7), (11). Segment A (3097 nucleotides) encodes a 106-kDa precursor polyprotein composed of pVP2-VP4-VP3, in that order, and a 15-kDa non-structural VP5 protein, found only in infected cells (14). VP2 and VP3 are the major capsid proteins, but VP2 is the major host-protective antigen of IPNV (9), (12).
There are commercial multivalent vaccines based on inactivated whole virus available as well as those produced with another approach, expressing VP2-derived conserved antigenic epitopes in bacteria for production of a subunit vaccine. In the laboratory, these current vaccines provide impressive protection against bath challenge with IPNV, but the behavior in the field is not predicted by the laboratory studies. This could be due to the lack of a well-defined challenge system with mortality as its endpoint. Results based on viral clearance exist but may not be as rigorous as a standardized challenge model (1). Another possible explanation could be that the salmon smolts or larger trout being vaccinated are already infected with the virus, as each year between 30-40% of the salmon hatcheries experience an outbreak of IPN (3) and IPN is endemic in many trout rearing areas. The need for better field efficacy could be achieved with improved vaccines that could be economically delivered to young salmonids such that subsequent vaccinations would boost existing immunity instead of trying to combat an existing acute or chronic infection.
USPTO Backgrounds
USPTO Backgrounds