首页> 外国专利> POLYNUCLEOTIDES ALLOWING THE EXPRESSION AND SECRETION OF RECOMBINANT HEPATITIS B SURFACE ANTIGEN (HBSAG) VIRUS-LIKE PARTICLES CONTAINING A FOREIGN PEPTIDE, THEIR PRODUCTION AND USE

POLYNUCLEOTIDES ALLOWING THE EXPRESSION AND SECRETION OF RECOMBINANT HEPATITIS B SURFACE ANTIGEN (HBSAG) VIRUS-LIKE PARTICLES CONTAINING A FOREIGN PEPTIDE, THEIR PRODUCTION AND USE

机译:允许含有外源肽的重组乙型肝炎表面抗原(HBSAG)病毒颗粒的表达和分泌的多核苷酸,其生产和使用

摘要

The hepatitis B surface antigen (HBsAg) can assemble into sub-virion virus like particles (VLPs). Vectors comprised of polynucleotides, identified as GA1xFlag-M and GA3xFlag-M, are provided for the expression of foreign proteins in such VLPs, and for release of the VLPs from host cells containing the vectors. In one example, an HIV-1 polyepitope-HBsAg recombinant fusion protein assembled into VLPs and was efficiently secreted. In another example, the successful expression of novel recombinant HIV-1/HBV virus-like particles (VLPs) in Nicotiana tabacum and Arabidopsis thaliana is described. The production levels and quality of the recombinant VLPs were comparable in the two plants, showing that parameters intrinsic to the recombinant proteins determined their assembly into VLPs. Theses recombinant transgenes represent an innovative tool to set up a bivalent anti-HIV-1/- HBV vaccine based on oral administration of crude extracts from transgenic plants. In a final example, it is demonstrated that by oral administration of transgenic plant crude extracts to humanized HSB mice it is possible to induce the activation of anti- HIV-1 specific CD8+ T cells in peripheral lymph nodes and spleen.
机译:乙型肝炎表面抗原(HBsAg)可以组装成亚病毒颗粒样颗粒(VLP)。提供了由标识为GA1xFlag-M和GA3xFlag-M的多核苷酸组成的载体,用于在这种VLP中表达外源蛋白质,以及从含有该载体的宿主细胞中释放VLP。在一实例中,HIV-1多表位-HBsAg重组融合蛋白组装成VLP并被有效地分泌。在另一个实例中,描述了在烟草和拟南芥中成功表达新型重组HIV-1 / HBV病毒样颗粒(VLP)。两种植物中重组VLP的生产水平和质量相当,表明重组蛋白固有的参数决定了它们组装成VLP的能力。这些重组转基因代表了一种创新工具,可基于口服转基因植物的粗提物来建立二价抗HIV-1 /-HBV疫苗。在最后的例子中,证明了通过将转基因植物粗提取物口服给予人源化HSB小鼠,可以诱导外周淋巴结和脾脏中抗HIV-1特异性CD8 + T细胞的活化。

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