IMMUNOGENICITY OF TRANSGENIC PLANT-DERIVED HEPATITIS-B SURFACE-ANTIGEN

IMMUNOGENICITY OF TRANSGENIC PLANT-DERIVED HEPATITIS-B SURFACE-ANTIGEN
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DOI:
10.1073/pnas.92.8.3358
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发表时间:
1995-04-11
影响因子:
11.1
通讯作者:
ARNTZEN, C
ARNTZEN, C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
THANAVALA, Y;YANG, YF;ARNTZEN, C

文献摘要

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儿童疫苗倡议的重点是鼓励发现使发展中国家更容易获得疫苗的技术。我们的策略是对植物进行基因工程改造,使它们可以作为生产亚单位抗原的发酵系统的廉价替代品。本文报道了从转基因烟草中纯化的重组B表面抗原(rHBsAg)在体内诱导的免疫应答。对烟草来源的rHBsAg的抗B肝炎应答与用酵母来源的rHBsAg(商品疫苗)免疫小鼠所获得的应答定性相似。此外,从用烟草衍生rHBsAg致敏的小鼠获得的T细胞可以在体外被烟草衍生rHBsAg、酵母衍生rHBsAg和代表位于HBsAg的S区(139-147)中的α决定簇的一部分的合成肽刺激。通过测试用单克隆抗独特型和抗独特型衍生肽刺激后致敏T细胞在体外增殖的能力,获得了对烟草衍生rHBsAg T细胞表位完整性的进一步支持,这两种肽都模拟了组特异性的a决定簇。总之,我们已经最终证明,当抗原在转基因植物中表达时,HBsAg的B细胞和T细胞表位都被保留。
The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves, The anti-hepatitis B response to the tobacco derived rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast-derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice primed with the tobacco-derived rHBsAg could be stimulated in vitro by the tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that represents part of the alpha determinant located in the S region (139-147) of HBsAg. Further support for the integrity of the T cell epitope of the tobacco-derived rHBsAg was obtained by testing the ability of the primed T Cells to proliferate in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype-derived peptide, both of which mimic the group-specific a determinant of HBsAg. In total, we have conclusively demonstrated that both B- and T-cell epitopes of HBsAg are preserved when the antigen is expressed in a transgenic plant.