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靶向合成人乳头瘤病毒(HPV)L2二硫键诱导的N端构象表位用于泛HPV疫苗开发

Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development.

作者信息

Khanal Sujita, Ferraris Eric Daniel, Zahin Maryam, Joh Joongho, Ghim Shin-je, Jenson Alfred Bennett

机构信息

Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA; James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA.

James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA; Emergency Medicine Associate, Vancouver, WA, USA.

出版信息

Exp Mol Pathol. 2015 Oct;99(2):330-4. doi: 10.1016/j.yexmp.2015.06.021. Epub 2015 Jun 30.

Abstract

BACKGROUND

Current vaccines against Human Papillomavirus (HPV) are highly effective and based on recombinant virus-like particles (VLPs) of the major capsid protein L1. Since these vaccines are HPV type-specific and expensive for global implementation, an alternative, broader-spectrum immunogen would be the N-terminus of the minor capsid protein L2 that induces low titered broadly cross-neutralizing antibodies. Here we analyzed the reactivity of different synthetic L2 peptides containing N-terminus amino acids 17-36 in order to test their antigenicity.

METHODS

Different synthetic peptides were designed to target the 17-36 amino acid sequences, present in highly antigenic amino-terminus of L2 protein. Six different peptides including Cys22-Cys28 disulfide bonded cyclized L2 peptide were examined for their antigenicity against mouse monoclonal antibody RG-1 and rabbit polyclonal antisera to HPV L2 by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Here we report that the cyclized form of synthetic L2 peptide, which is formed through Cys22-Cys28 disulfide bridges, has the highest reactivity to antibodies than other synthetic L2 peptides.

CONCLUSION

A cyclized L2 peptide has potential to be an excellent candidate to formulate a low-cost, broadly protective pan-oncogenic HPV vaccine.

摘要

背景

目前的人乳头瘤病毒(HPV)疫苗非常有效,基于主要衣壳蛋白L1的重组病毒样颗粒(VLP)。由于这些疫苗是HPV型特异性的,且全球推广成本高昂,一种替代的、广谱免疫原将是次要衣壳蛋白L2的N端,它能诱导低滴度的广泛交叉中和抗体。在此,我们分析了不同的包含N端氨基酸17 - 36的合成L2肽的反应性,以测试它们的抗原性。

方法

设计不同的合成肽靶向L2蛋白高抗原性N端存在的17 - 36氨基酸序列。通过酶联免疫吸附测定(ELISA)检测六种不同的肽,包括Cys22 - Cys28二硫键连接的环化L2肽,针对小鼠单克隆抗体RG - 1和抗HPV L2兔多克隆抗血清的抗原性。

结果

我们在此报告,通过Cys22 - Cys28二硫键形成的合成L2肽环化形式,与其他合成L2肽相比,对抗体具有最高的反应性。

结论

环化L2肽有潜力成为一种优秀的候选物,用于制备低成本、广泛保护性的泛致癌HPV疫苗。

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