Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development
Targeting synthetic Human Papillomavirus (HPV) L2 disulfide-induced N-terminus conformational epitopes for pan-HPV vaccine development
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DOI：
10.1016/j.yexmp.2015.06.021
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发表时间：
2015-10-01
影响因子：
3.6
通讯作者：
Jenson, Alfred Bennett
中科院分区：
文献类型：
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作者：
Khanal, Sujita;Ferraris, Eric Daniel;Jenson, Alfred Bennett
背景：目前针对人乳头瘤病毒（HPV）的疫苗是高效的，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类型特异性的，并且在全球实施时价格昂贵，因此另一种更广泛的免疫原将是次要衣壳蛋白L2的n端，可诱导低滴度的广泛交叉中和抗体。本文分析了含n端氨基酸17-36的不同合成L2肽的反应性，以测试其抗原性。方法：针对L2蛋白高抗原氨基端存在的17-36个氨基酸序列，设计不同的合成肽。采用酶联免疫吸附试验（ELISA）检测了包括Cys22-Cys28二硫键环化L2肽在内的6种不同多肽对小鼠单克隆抗体RG-1和兔HPV 12多克隆抗血清的抗原性。结果：本文报道了通过Cys22-Cys28二硫桥形成的合成12肽环化形式对抗体的反应性高于其他合成L2肽。结论：环化L2肽有潜力成为低成本、广泛保护的泛致癌HPV疫苗的极好候选物。(C) 2015出版的爱思唯尔公司。
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 12 by enzyme-linked immunosorbent assay (ELISA).Results: Here we report that the cyclized form of synthetic 12 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. (C) 2015 Published by Elsevier Inc.