A papillomavirus-like particle (VLP) vaccine displaying HPV16 L2 epitopes induces cross-neutralizing antibodies to HPV11.
A papillomavirus-like particle (VLP) vaccine displaying HPV16 L2 epitopes induces cross-neutralizing antibodies to HPV11.
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DOI：
10.1016/j.vaccine.2006.11.049
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发表时间：
2007-03-01
期刊：
影响因子：
5.5
通讯作者：
Kirnbauer R
中科院分区：
文献类型：
--
作者：
Slupetzky K;Gambhira R;Culp TD;Shafti-Keramat S;Schellenbacher C;Christensen ND;Roden RB;Kirnbauer R
乳头瘤病毒L2次要衣壳蛋白的肽可以诱导中和广泛的人乳头瘤病毒（HPV）基因型的抗体（Ab）。不幸的是，在病毒衣壳中，L2的抗原性低于L1。为了诱导对其他粘膜类型具有交叉中和活性的强抗L2 Ab应答，产生嵌合病毒样颗粒（VLP），其中HPV 16 L2中和表位（包含L2残基69-81或108-120）插入牛乳头瘤病毒1型（BPV 1）的L1主要衣壳蛋白的免疫显性表面环（残基133和134之间）内。这些嵌合体自组装成五聚体壳粒，或类似于野生型（wt）L1蛋白的完整VLP。用组装的颗粒制剂免疫兔诱导L2特异性血清Ab，其滴度比与KLH偶联的同源合成L2肽诱导的滴度高10倍。两种嵌合蛋白的抗血清部分中和了HPV 16假病毒体，证实了两种HPV 16 L2肽都定义了中和表位。当分析通过真实HPV 11病毒体交叉中和感染的能力时，使用通过RT-PCR测定法检测早期病毒RNA作为读数，针对包含L2残基69-81而非108-120的嵌合蛋白的免疫血清是部分中和的。此外，通过用合成L2肽108-120而不是69-81接种诱导的小鼠抗血清在该测定中是部分中和的。通过嵌合VLP上展示的L2表位诱导交叉中和Ab代表了产生广谱疫苗以保护免受相关粘膜HPV和相关瘤形成的可能策略。
Peptides of the papillomavirus L2 minor capsid protein can induce antibodies (Ab) that neutralize a broad range of human papillomavirus (HPV) genotypes. Unfortunately, L2 is antigenically subdominant to L1 in the virus capsid. To induce a strong anti-L2 Ab response with cross-neutralizing activity to other mucosal types, chimeric virus-like particles (VLP) were generated in which HPV16 L2 neutralization epitopes (comprising L2 residues 69–81 or 108–120) are inserted within an immunodominant surface loop (between residues 133 and 134) of the L1 major capsid protein of bovine papillomavirus type 1 (BPV1). These chimeras self-assembled into pentameric capsomers, or complete VLP similar to wild type (wt) L1 protein. Immunization of rabbits with assembled particle preparations induced L2-specific serum Ab with titers 10-fold higher than those induced by cognate synthetic L2 peptides coupled to KLH. Antisera to both chimeric proteins partially neutralized HPV16 pseudovirions, confirming that both HPV16 L2 peptides define neutralization epitopes. When analyzed for the ability to cross-neutralize infection by authentic HPV11 virions, using detection of early viral RNA by RT-PCR-assays as the readout, immune serum to chimeric protein comprising L2 residues 69–81, but not 108–120, was partially neutralizing. In addition, mouse-antiserum induced by vaccinations with synthetic L2 peptide 108–120, but not 69–81, was partially neutralizing in this assay. Induction of cross-neutralization Ab by L2 epitopes displayed on chimeric VLP represents a possible strategy for the generation of broad-spectrum vaccines to protect against relevant mucosal HPV and associated neoplasia.
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