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重组绵羊白细胞介素-1β作为免疫佐剂的生产及体内应用

Production and in vivo use of recombinant ovine IL-1 beta as an immunological adjuvant.

作者信息

Andrews A E, Lofthouse S A, Bowles V M, Brandon M R, Nash A D

机构信息

Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Vaccine. 1994 Jan;12(1):14-22. doi: 10.1016/0264-410x(94)90005-1.

DOI:10.1016/0264-410x(94)90005-1
PMID:8303935
Abstract

To determine the potential of ovine interleukin 1 (IL-1) as a vaccine adjuvant in sheep, we have expressed and purified recombinant ovine IL-1 beta (rovIL-1 beta) from bacterial cultures using a modified form of the ovine IL-1 beta cDNA. Adjuvant trials using the model protein avidin demonstrated that rovIL-1 beta when administered in association with a compound providing a slow-release mechanism, resulted in significant enhancement of specific serum antibody levels in both mice and sheep. In a dose-response experiment in sheep, intradermal immunization with avidin plus either 10 or 100 micrograms of rovIL-1 beta in aluminium hydroxide resulted in antibody levels four- to eightfold higher than immunizations without rovIL-1 beta. The addition of rovIL-1 beta also resulted in a more severe DTH response to avidin indicating that rovIL-1 beta is able to enhance both humoral and cell-mediated responses to avidin. The highest antibody titres were observed when sheep received rovIL-1 beta in both the primary and secondary immunizations although the addition of rovIL-1 beta in only one of the immunizations still resulted in a significant increase in antibody levels. Additional experiments showed that rovIL-1 beta and avidin must be administered in a site drained by the same lymph node for the adjuvant effect of rovIL-1 beta to be observed.

摘要

为了确定绵羊白细胞介素1(IL-1)作为绵羊疫苗佐剂的潜力,我们使用改良形式的绵羊IL-1β cDNA从细菌培养物中表达并纯化了重组绵羊IL-1β(rovIL-1β)。使用模型蛋白抗生物素蛋白进行的佐剂试验表明,当rovIL-1β与提供缓释机制的化合物联合给药时,可显著提高小鼠和绵羊体内特异性血清抗体水平。在绵羊的剂量反应实验中,用抗生物素蛋白加10或100微克rovIL-1β在氢氧化铝中进行皮内免疫,产生的抗体水平比未加rovIL-1β的免疫高4至8倍。添加rovIL-1β还导致对抗生物素蛋白的迟发型超敏反应(DTH)更强烈,表明rovIL-1β能够增强对抗生物素蛋白的体液免疫和细胞介导免疫反应。当绵羊在初次和二次免疫中都接受rovIL-1β时,观察到最高的抗体滴度,尽管仅在一次免疫中添加rovIL-1β仍导致抗体水平显著增加。额外的实验表明,为了观察到rovIL-1β的佐剂效果,rovIL-1β和抗生物素蛋白必须在同一个淋巴结引流的部位给药。

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