A novel technology for the production of a heterologous lipoprotein immunogen in high yield has implications for the field of vaccine design
A novel technology for the production of a heterologous lipoprotein immunogen in high yield has implications for the field of vaccine design
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DOI：
10.1016/j.vaccine.2008.12.043
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发表时间：
2009-02-25
期刊：
影响因子：
5.5
通讯作者：
Leng, Chih-Hsiang
中科院分区：
文献类型：
--
作者：
Chen, Hsin-Wei;Liu, Shih-Jen;Leng, Chih-Hsiang
我们已经开发了一种新的平台技术，可以表达具有内在佐剂特性的高水平重组脂蛋白。在这项研究中，利用大肠杆菌菌株C43 （DE3）可以高产地生产Ag473（一种来自脑膜炎奈瑟菌的脂蛋白）。通过将来自登革热病毒的非脂免疫原（E3）与来自其他脂蛋白的不同脂质信号肽以及不同长度的Ag473片段融合，我们发现融合序列必须至少包含Ag473的n端40个残基D1，才能实现重组脂免疫原（rlipod1e3）的高表达。在动物实验中发现，rlipo-D1E3比单独使用rE3或与明矾佐剂配制的rE3产生更强的抗e3和病毒中和抗体反应。这些结果成功地证明了脂质免疫原在新型疫苗开发中的优点。(C) 2008 Elsevier Ltd版权所有。
We have developed a novel platform technology that can express high levels of recombinant lipoproteins with intrinsic adjuvant properties. In this study, Ag473 (a lipoprotein from Neisseria meningitidis) can be produced in high yields using Escherichia coli strain C43 (DE3). After testing a non-lipoimmunogen (E3, from dengue virus) fused with different lipid signal peptides from other lipoproteins as well as Ag473 fragments of different lengths, we identified that the fusion sequence has to contain at least the N-terminal 40 residues, D1, of Ag473 to achieve high expression levels of the recombinant lipo-immunogen (rlipo-D1E3). The rlipo-D1E3 was found to elicit stronger anti-E3 and virus neutralizing antibody responses in animal studies than those from rE3 alone or rE3 formulated with alum adjuvant. These results have successfully demonstrated the merit of lipo-immunogens for novel vaccine development. (C) 2008 Elsevier Ltd. All rights reserved.