Koppang Erling O, Bjerkås Inge, Haugarvoll Erlend, Chan Edward K L, Szabo Nancy J, Ono Nobutaka, Akikusa Bunshiro, Jirillo Emilio, Poppe Trygve T, Sveier Harald, Tørud Brit, Satoh Minoru
Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Ullevålsveien 72, Oslo, Norway.
J Immunol. 2008 Oct 1;181(7):4807-14. doi: 10.4049/jimmunol.181.7.4807.
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.
全球消费的三文鱼超过一半是养殖的。油佐剂疫苗引入三文鱼养殖,通过预防感染使大规模生产成为可能。腹腔注射的疫苗含有矿物油等油佐剂。然而,在啮齿动物中,单次腹腔注射佐剂烃油会诱发狼疮样系统性自身免疫综合征,其特征为自身抗体、免疫复合物性肾小球肾炎和关节炎。在本研究中,检测了接受油佐剂疫苗的养殖三文鱼是否具有与注射佐剂油的啮齿动物相似的自身免疫综合征。从接种或未接种疫苗的大西洋三文鱼(实验对象,七个养殖场)以及野生三文鱼中采集血清和组织。检测血清中的自身抗体(免疫荧光、酶联免疫吸附测定和免疫沉淀法)和IgM水平(酶联免疫吸附测定)。检查肾脏和肝脏的病理情况。与未接种疫苗的对照相比,接种疫苗的鱼体内常见自身抗体,这些抗体除了与哺乳动物抗原发生反应外,还与三文鱼细胞/抗原发生反应。免疫荧光中弥漫性核/细胞质染色很常见,但有些具有更特异的模式。接种疫苗的鱼血清总IgM水平也有所升高;然而,自身抗体的升高倍数远高于总IgM。接种疫苗的鱼的血清能免疫沉淀铁蛋白,约50%的血清还与其他独特蛋白质发生反应。接种疫苗的鱼肝脏中常见血栓形成和肉芽肿性炎症以及免疫复合物性肾小球肾炎。在接种疫苗的养殖大西洋三文鱼中,类似于佐剂油诱导的狼疮小鼠模型的自身免疫现象很常见。这可能对生产损失、病因不明的疾病以及未来的疫苗和三文鱼养殖策略产生重大影响。