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一种针对鲑鱼立克次氏体病原体鲑鱼立克次氏体的有效重组亚单位疫苗。

An efficacious recombinant subunit vaccine against the salmonid rickettsial pathogen Piscirickettsia salmonis.

作者信息

Kuzyk M A, Burian J, Machander D, Dolhaine D, Cameron S, Thornton J C, Kay W W

机构信息

Canadian Bacterial Diseases Network, Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055, British Columbia V8W 3P6, Victoria, Canada.

出版信息

Vaccine. 2001 Mar 21;19(17-19):2337-44. doi: 10.1016/s0264-410x(00)00524-7.

Abstract

Piscirickettsia salmonis is the aetiological agent of salmonid rickettsial septicaemia, an economically devastating rickettsial disease of farmed salmonids. Infected salmonids respond poorly to antibiotic treatment and no effective vaccine is available for the control of P. salmonis. Bacterin preparations of P. salmonis were found to elicit a dose-dependent response in coho salmon (Oncorhynchus kisutch), which varied from inadequate protection to exacerbation of the disease. However, an outer surface lipoprotein of P. salmonis, OspA, recombinantly produced in Escherichia coli elicited a high level of protection in vaccinated coho salmon with a relative percent survival as high as 59% for this single antigen. In an effort to further improve the efficacy of the OspA recombinant vaccine, T cell epitopes (TCE's) from tetanus toxin and measles virus fusion protein, that are universally immunogenic in mammalian immune systems, were incorporated tandemly into an OspA fusion protein. Addition of these TCE's dramatically enhanced the efficacy of the OspA vaccine, reflected by a three-fold increase in vaccine efficacy. These results represent a highly effective monovalent recombinant subunit vaccine for a rickettsia-like pathogen, P. salmonis, and for the first time demonstrate the immunostimulatory effect of mammalian TCE's in the salmonid immune model. These results may also be particularly pertinent to salmonid aquaculture in which the various subspecies are outbred and of heterologous haplotypes.

摘要

鲑鱼立克次氏体是鲑鱼立克次氏体败血症的病原体,这是一种对养殖鲑鱼具有经济毁灭性的立克次氏体疾病。受感染的鲑鱼对抗生素治疗反应不佳,且尚无有效的疫苗可用于控制鲑鱼立克次氏体。研究发现,鲑鱼立克次氏体的菌苗制剂在银大麻哈鱼(Oncorhynchus kisutch)中引发剂量依赖性反应,反应程度从保护不足到疾病加重不等。然而,在大肠杆菌中重组产生的鲑鱼立克次氏体的一种外表面脂蛋白OspA,在接种疫苗的银大麻哈鱼中引发了高水平的保护作用,仅这一种抗原的相对存活率就高达59%。为了进一步提高OspA重组疫苗的效力,将在哺乳动物免疫系统中普遍具有免疫原性的破伤风毒素和麻疹病毒融合蛋白的T细胞表位(TCE)串联整合到一种OspA融合蛋白中。添加这些TCE显著提高了OspA疫苗的效力,疫苗效力提高了三倍就反映了这一点。这些结果代表了一种针对类立克次氏体病原体鲑鱼立克次氏体的高效单价重组亚单位疫苗,并且首次证明了哺乳动物TCE在鲑鱼免疫模型中的免疫刺激作用。这些结果可能也与鲑鱼养殖特别相关,因为鲑鱼的各个亚种是远交的且具有异源单倍型。

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