Thanavala Y, Yang Y F, Lyons P, Mason H S, Arntzen C
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3358-61. doi: 10.1073/pnas.92.8.3358.
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 a 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.
儿童疫苗倡议的重点是鼓励研发能让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，使其可作为生产亚单位抗原的发酵系统的廉价替代品。在本文中，我们报告了使用从转基因烟草叶中纯化的重组乙型肝炎表面抗原（rHBsAg）在体内引发的免疫反应。对烟草来源的rHBsAg的抗乙型肝炎反应在质量上与用酵母来源的rHBsAg（商业疫苗）免疫小鼠所获得的反应相似。此外，用烟草来源的rHBsAg致敏的小鼠获得的T细胞在体外可被烟草来源的rHBsAg、酵母来源的rHBsAg以及代表位于HBsAg S区（139 - 147）的α决定簇一部分的合成肽刺激。通过测试致敏的T细胞在用单克隆抗独特型抗体和抗独特型衍生肽刺激后在体外增殖的能力，进一步支持了烟草来源的rHBsAg的T细胞表位的完整性，这两种物质都模拟了HBsAg的群特异性α决定簇。总之，我们已经确凿地证明，当抗原在转基因植物中表达时，HBsAg的B细胞和T细胞表位均得以保留。
