Expression, purification and immunogenic characterization of hepatitis C virus recombinant E1E2 protein expressed by Pichia pastoris yeast

Expression, purification and immunogenic characterization of hepatitis C virus recombinant E1E2 protein expressed by Pichia pastoris yeast
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DOI:
10.1016/j.antiviral.2010.07.007
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发表时间:
2010-10-01
期刊:
影响因子:
7.6
通讯作者:
She, Yinglong
She, Yinglong
中科院分区:
医学2区
文献类型:
--
作者:
Cai, Weijia;Su, Liya;She, Yinglong

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开发有效的疫苗可能是控制丙型肝炎病毒(HCV)感染的关键。最近的研究表明,HCV包膜蛋白可以诱导针对HCV保守结构域的广泛中和抗体与细胞受体结合。因此,HCV包膜蛋白被认为是HCV疫苗的主要候选蛋白。本研究利用毕赤酵母表达了截短型HCV E1 E2蛋白,该蛋白由E1残基187-346和E2残基381-699组成。该酵母菌能高效表达重组HCV E1 E2蛋白。该蛋白质具有复杂的糖基化,并可结合到CD 81,推定的HCV受体。此外,纯化的蛋白质可以在兔中有效地诱导抗E1 E2抗体,该抗体能够中和来自HCV基因型1a和1b的两种HCV假型颗粒以及来自HCV基因型2a的HCV病毒体。这些发现表明重组E1 E2糖蛋白可有效诱导广泛中和抗体,是一种有效的HCV疫苗候选物。(C)出版社:Elsevier B. V.
Development of an effective vaccine may be the key in the control of hepatitis C virus (HCV) infection. Recent studies have shown that HCV envelope proteins can induce broadly neutralizing antibodies against conserved domain for HCV binding to the cellular receptors. So HCV envelope proteins are considered as the major HCV vaccine candidate. In this study, we used Pichia pastoris yeast to express truncated HCV E1E2 protein, which consists of E1 residues 187-346 and E2 residues 381-699. The yeast can produce high level of recombinant HCV E1E2 protein. The protein has complex glycosylation and can bind to CD81, the putative HCV receptor. Moreover, the purified protein can efficiently induce anti-E1E2 antibodies in rabbits, which are able to neutralize two kinds of HCV pseudotype particles derived from HCV genotype 1a and 1b, as well as HCV virions derived from HCV genotype 2a. These findings indicate that the recombinant E1E2 glycoprotein is effective in inducing broadly neutralizing antibodies, and is a potent HCV vaccine candidate. (C) 2010 Published by Elsevier B.V.