title: Vaccination-induced systemic autoimmunity in farmed Atlantic salmon.
abstract: Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single i.p. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected rodents was examined. Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and approximately 50% also reacted with other unique proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Ullevålsveien 72, Oslo, Norway.
authors.forename: Erling O
authors.initials: EO
authors.lastname: Koppang
authors.forename: Inge
authors.initials: I
authors.lastname: Bjerkås
authors.forename: Erlend
authors.initials: E
authors.lastname: Haugarvoll
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Szabo
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ono
authors.forename: Bunshiro
authors.initials: B
authors.lastname: Akikusa
authors.forename: Emilio
authors.initials: E
authors.lastname: Jirillo
authors.forename: Trygve T
authors.initials: TT
authors.lastname: Poppe
authors.forename: Harald
authors.initials: H
authors.lastname: Sveier
authors.forename: Brit
authors.initials: B
authors.lastname: Tørud
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000097:blood; D017756:Aquaculture / Q000379:methods; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007105:Immune Complex Diseases / Q000276:immunology / Q000517:prevention & control; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D020014:K562 Cells; D008107:Liver Diseases / Q000276:immunology / Q000517:prevention & control; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008899:Mineral Oil / Q000008:administration & dosage / Q000009:adverse effects; D011897:Random Allocation; D020317:Salmo salar / Q000276:immunology*; D020246:Venous Thrombosis / Q000276:immunology / Q000517:prevention & control; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D001428:Bacterial Vaccines; D007075:Immunoglobulin M; D014765:Viral Vaccines; D008899:Mineral Oil