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将爱泼斯坦-巴尔病毒gp350表达为用于EBV亚单位疫苗的单链糖蛋白。

Expression of Epstein-Barr virus gp350 as a single chain glycoprotein for an EBV subunit vaccine.

作者信息

Jackman W T, Mann K A, Hoffmann H J, Spaete R R

机构信息

Aviron, Mountain View, CA 94043, USA.

出版信息

Vaccine. 1999 Feb 26;17(7-8):660-8. doi: 10.1016/s0264-410x(98)00248-5.

DOI:10.1016/s0264-410x(98)00248-5
PMID:10067671
Abstract

There is currently no commercially available vaccine for Epstein Barr virus (EBV)-related disease in humans. Since the EBV glycoprotein gp350/220 is the primary target for EBV-neutralizing antibodies following natural infection in humans and some forms of gp350/220 have been shown to protect against EBV-related disease in animal models, it is a likely candidate for an EBV subunit vaccine. We have made gp350/220 gene constructs that facilitate gp350 secretion from CHO cells and created splice site mutations in the gene that effectively prevent production of the gp220 species. Recombinant CHO cell gp350 (MSTOP gp350) is recognized by several different anti-gp350/220 monoclonal antibodies, and is also competent to bind to the cellular EBV receptor, CD21, suggesting that the recombinant protein is conformationally similar to wild-type EBV gp350/220. The MSTOP gp350 antigen raises high antibody titers in rabbits and these antibodies neutralize wild-type EBV. These properties make MSTOP gp350 a realistic candidate for a subunit vaccine against EBV-related disease.

摘要

目前尚无用于人类埃博拉病毒(EBV)相关疾病的商业可用疫苗。由于EBV糖蛋白gp350/220是人类自然感染后EBV中和抗体的主要靶点,并且某些形式的gp350/220已在动物模型中显示出对EBV相关疾病具有保护作用,因此它是EBV亚单位疫苗的一个可能候选物。我们构建了gp350/220基因构建体,以促进gp350从CHO细胞中分泌,并在该基因中产生剪接位点突变,从而有效阻止gp220亚型的产生。重组CHO细胞gp350(MSTOP gp350)可被几种不同的抗gp350/220单克隆抗体识别,并且还能够与细胞EBV受体CD21结合,这表明重组蛋白在构象上与野生型EBV gp350/220相似。MSTOP gp350抗原在兔体内可引发高抗体滴度,并且这些抗体可中和野生型EBV。这些特性使MSTOP gp350成为抗EBV相关疾病亚单位疫苗的一个现实候选物。

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