Virus Reference Department, Public Health England, London, UK.
Sci Rep. 2016 Dec 22;6:39730. doi: 10.1038/srep39730.
The human papillomavirus (HPV) vaccines consist of major capsid protein (L1) virus-like particles (VLP) and are highly efficacious against the development of cervical cancer precursors attributable to oncogenic genotypes, HPV16 and HPV18. A degree of vaccine-induced cross-protection has also been demonstrated against genetically-related genotypes in the Alpha-7 (HPV18-like) and Alpha-9 (HPV16-like) species groups which is coincident with the detection of L1 cross-neutralising antibodies. In this study the L1 domains recognised by inter-genotype cross-neutralising antibodies were delineated. L1 crystallographic homology models predicted a degree of structural diversity between the L1 loops of HPV16 and the non-vaccine Alpha-9 genotypes. These structural predictions informed the design of chimeric pseudovirions with inter-genotype loop swaps which demonstrated that the L1 domains recognised by inter-genotype cross-neutralising antibodies comprise residues within the DE loop and the late region of the FG loop. These data contribute to our understanding of the L1 domains recognised by vaccine-induced cross-neutralising antibodies. Such specificities may play a critical role in vaccine-induced cross-protection.
人类乳头瘤病毒（HPV）疫苗由主要衣壳蛋白（L1）病毒样颗粒（VLP）组成，对由致癌基因型 HPV16 和 HPV18 引起的宫颈癌前病变的发展具有高度疗效。研究还表明，疫苗诱导的交叉保护作用在与 Alpha-7（HPV18 样）和 Alpha-9（HPV16 样）种系组中遗传相关的基因型中也存在，这与 L1 交叉中和抗体的检测一致。在这项研究中，确定了由不同基因型交叉中和抗体识别的 L1 结构域。L1 晶体学同源模型预测 HPV16 的 L1 环与非疫苗 Alpha-9 基因型之间存在一定程度的结构多样性。这些结构预测为具有不同基因型环交换的嵌合假病毒的设计提供了信息，证明了不同基因型交叉中和抗体识别的 L1 结构域包括 DE 环和 FG 环晚期区域内的残基。这些数据有助于我们了解疫苗诱导的交叉中和抗体识别的 L1 结构域。这些特异性可能在疫苗诱导的交叉保护中发挥关键作用。
