title: Salmonid alphavirus-based replicon vaccine against infectious salmon anemia (ISA): impact of immunization route and interactions of the replicon vector.
abstract: A salmonid alphavirus (SAV)-based replicon encoding the infectious salmon anemia virus (ISAV) hemagglutinin-esterase (HE), pSAV/HE, is an efficacious vaccine against infectious salmon anemia (ISA). Delivered intramuscularly (i.m.), the replicon vaccine provides high protection against subsequent ISAV challenge in Atlantic salmon (Salmo salar), and induces a strong innate response locally at the injection site. This may be beneficial and could warrant reduced doses and improved efficacy compared to conventional DNA vaccines. In the present study, we found that intraperitoneal (i.p.) administration of the pSAV/HE replicon vaccine did not induce protection, neither alone or in combination with a sub-potent, inactivated low-dose ISAV vaccine given i.p. No significant differences between the two immunization routes regarding systemic immune responses could be observed. I.m. injection of the replicon vector encoding a non-viral gene or the protective glycoprotein (G protein) from the heterologous viral hemorrhagic septicemia virus (VHSV) induced no protection against ISA. Although the replicons without the ISAV HE did induce IFN-signaling pathways at the muscle injection site similar to the pSAV/HE replicon they did not improve the efficacy of a sub-potent inactivated low-dose ISAV vaccine delivered i.p. Moreover, there was a tendency for reduced efficacy of the pSAV/HE replicon vaccine injected i.m. when co-injected with the replicon encoding the VHSV G protein, which previously, after DNA vaccination, have been reported to induce cross-protection against heterologous virus challenge in fish.
authors.affiliation: Department of Food Safety and Infection Biology, The Norwegian School of Veterinary Science, P.O. 8146 Dep, N-0033 Oslo, Norway. Electronic address: astrid.wolf@nvh.no.
authors.forename: Astrid
authors.initials: A
authors.lastname: Wolf
authors.affiliation: MSD Animal Health Innovation AS, Thormøhlensgate 55, N-5008 Bergen, Norway. Electronic address: kjartan.hodneland@merck.com.
authors.forename: Kjartan
authors.initials: K
authors.lastname: Hodneland
authors.affiliation: MSD Animal Health Innovation AS, Thormøhlensgate 55, N-5008 Bergen, Norway. Electronic address: petter.frost@merck.com.
authors.forename: Petter
authors.initials: P
authors.lastname: Frost
authors.affiliation: MSD Animal Health BV, P.O. Box 31, 5830 AA Boxmeer, The Netherlands. Electronic address: mathieu.hoeijmakers@merck.com.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Hoeijmakers
authors.affiliation: Department of Food Safety and Infection Biology, The Norwegian School of Veterinary Science, P.O. 8146 Dep, N-0033 Oslo, Norway. Electronic address: espen.rimstad@nvh.no.
authors.forename: Espen
authors.initials: E
authors.lastname: Rimstad
mesh_terms: D000524:Alphavirus / Q000276:immunology*; D000818:Animals; D005393:Fish Diseases / Q000517:prevention & control* / Q000821:virology; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism; D007273:Injections, Intramuscular / Q000662:veterinary; D007274:Injections, Intraperitoneal / Q000662:veterinary; D046829:Isavirus / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000662:veterinary* / Q000821:virology; D012093:Replicon; D020317:Salmo salar / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D006389:Hemagglutinins, Viral; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; C060814:hemagglutinin esterase
keywords: Immunization against infectious salmon anemia; Immunization route of DNA vaccines in fish; Replicon-induced immune responses in Atlantic salmon; Salmonid alphavirus-based replicon vaccine