HPV11 mutant virus-like particles elicit immune responses that neutralize virus and delineate a novel neutralizing domain
HPV11 mutant virus-like particles elicit immune responses that neutralize virus and delineate a novel neutralizing domain
复制标题
DOI：
10.1006/viro.1999.0083
复制
发表时间：
2000-01-20
期刊：
影响因子：
3.7
通讯作者：
Christensen, ND
中科院分区：
文献类型：
--
作者：
Ludmerer, SW;McClements, WL;Christensen, ND
人乳头瘤病毒（HPV）引起中和免疫反应的区域的表征支持对病毒感染性的研究，并为预防性疫苗的开发和评价提供了见解。HPV 11是生殖器疣的主要病原体，也是一种可能的疫苗候选者。三种中和性单克隆抗体（mAb）结合的构象依赖性表位已定位于L1主要衣壳蛋白的残基G（131）T（132）。只有当L1组装成病毒体或模拟衣壳结构的病毒样颗粒（VLP）时，mAb才会结合L1。我们有兴趣确定其他领域的L1引起中和反应。为此，我们已经产生了一组针对源自HPV 11 L1的VLP的mAb，所述VLP具有G131 S置换。新的mAb与先前定位于残基G（131）T（132）的中和mAb不同，因为它们结合原型和HPV 11：G131 S突变VLP。部分新的单克隆抗体在体外中和病毒。我们已经绘制了这些新的单克隆抗体，以及针对HPV 11病毒体产生的中和单克隆抗体的表位，通过测量与HPV 6 VLP的结合，这些VLP被HPV 11样氨基酸取代。两个区域是关键的：一个由HPV 11 L1残基263-290限定，另一个由残基346-349限定。mAb H11.H3和H11.G131S.G3结合具有源自346-349区域的取代的HPV 6 VLP;此外，H11.G131S.G3结合具有仅源自263-290区域的取代的HPV 6 VLP。尽管H11.H3不结合具有源自263-290区的取代的HPV 6 VLP，但当两组取代都存在时，与HPV 6 VLP的结合增强。mAb H11.G131S.11和H11.G131S.K5结合具有263-290个取代的HPV 6 VLP，但显示与具有346-349个取代的HPV 6 VLP几乎没有结合。然而，当两个区域都存在取代时，与HPV 6 VLP的结合增强。346-349区域以前没有被描述为引起任何HPV类型的中和反应。此外，这项工作还证明了L1的两个不同区域所贡献的复杂结合位点。(C)北京大学出版社.
Characterization of the regions of human papillomaviruses (HPVs) that elicit neutralizing immune responses supports studies on viral infectivity and provides insight for the development and evaluation of prophylactic vaccines. HPV11 is a major etiologic agent of genital warts and a likely vaccine candidate. A conformationally dependent epitope for the binding of three neutralizing monoclonal antibodies (mAbs) has been mapped to residues G(131)T(132) of the L1 major capsid protein. The mAbs bind L1 only when it is assembled into virions or into virus-like particles (VLPs) that mimic the capsid structure. We were interested in identifying other domains of L1 that elicit neutralizing responses. To this end, we have generated a panel of mAbs against VLPs derived from HPV11 L1 harboring a G131S substitution. The new mAbs are unlike the neutralizing mAbs previously mapped to residues G(131)T(132) in that they bind both prototype and HPV11:G131S mutant VLPs. Some of the new mAbs neutralized virus in vitro. We have mapped epitopes for three of these new mAbs, as well as a neutralizing mAb generated against HPV11 virions, by measuring binding to HPV6 VLPs substituted with HPV11-like amino acids. Two regions are critical: one defined by HPV11 L1 residues 263-290 and the other by residues 346-349. mAbs H11.H3 and H11.G131S.G3 bind HPV6 VLPs with substitutions derived from the 346-349 region; in addition, H11.G131S.G3 binds HPV6 VLPs with substitutions derived only from the 263-290 region. Although H11.H3 does not bind HPV6 VLPs with substitutions derived from the 263-290 region, binding to HPV6 VLPs is enhanced when both sets of substitutions are present. mAbs H11.G131S.11 and H11.G131S.K5 bind HPV6 VLPs with the 263-290 substitutions, but show little binding to HPV6 VLPs with the 346-349 substitutions. However, binding to HPV6 VLPs is enhanced when substitutions at both regions are present. The 346-349 region has not previously been described as eliciting a neutralizing response for any HPV type. In addition, the work demonstrates a complex binding site contributed by two distinct regions of L1. (C) 2000 Academic Press.