HPV Serology

人乳头瘤病毒感染大多是良性和自限性的，但某些基因型被认为是高风险和致癌的。几乎所有的宫颈癌中都发现了HPV，其中HPV 16占50%，HPV 18占20%。目前，有三种获得许可的人乳头瘤病毒（HPV）疫苗具有优异的疗效，但疫苗诱导免疫的相关性特征不佳。其中一种疫苗是二价的（Cervarix，GSK），第二种是四价的（Gardasil，Merck），而第三种是九价的（Gardasil 9）。所有三种疫苗都利用基于HPV的L1主要衣壳蛋白的病毒样颗粒（VLP）。VLP是非感染性蛋白质衣壳，其可以通过在酵母或昆虫细胞中表达衣壳蛋白来产生。重组L1衣壳蛋白组装成60 nm HPV VLP。每种疫苗的效力都是用不同的标准进行评估的，因此很难对疫苗进行比较。也有迹象表明，这些疫苗的一剂可能与目前使用的三剂方案一样有效，但没有一套血清学标准可用于评价。目前，合并的人血清用作最佳标准品，并用于创建曲线，根据该曲线以任意单位/ml外推结果。然而，合并血清是一种有限的资源，后续研究需要开发一种新的合并液，该合并液根据先前的合并液进行校准，因此作为标准品存在局限性。目标是建立一个实验室，通过开发可供科学界使用的经验证的试剂和标准品，使人类乳头瘤病毒（HPV）抗体检测的血清学测定标准化和协调化。该实验室将提供符合疫苗开发和实施规定的监管要求的合格和标准化的高通量检测。该实验室将与科学界和监管机构合作，以确定HPV血清学中未满足的需求。

Human Papillomavirus infection is mostly benign and self-limiting, however certain genotypes are considered high risk and oncogenic. HPV has been found in virtually all cervical cancers with HPV 16 causing 50% and HPV 18 another 20%. Currently, there are three licensed human papillomavirus (HPV) vaccines with excellent efficacy, but poorly characterized correlates of vaccine induced immunity. One of the vaccines is bivalent (Cervarix, GSK), the second is quadrivalent (Gardasil, Merck), while the third is nonavalent (Gardasil9). All three vaccines utilize virus like particles (VLPs) based on the L1 major capsid protein from HPV. VLPs are noninfectious protein capsids which can be produced by expressing the capsid protein in yeast or insect cells. The recombinant L1 capsid protein assembles in into the 60-nm HPV VLP. The efficacy of each vaccine has been evaluated with different standards, making comparison of the vaccines difficult. There has also been indication suggesting that one dose of these vaccines may be as efficacious as the three-dose regimen currently in use, however there is no set of serological standards that could be used for evaluation. Currently, pooled human serum serves as the best standard and is used to create a curve from which results are extrapolated in arbitrary Units/ml. However, the pooled serum is a finite resource and subsequent studies require the development of a new pool that is calibrated against the previous pool and therefore has its limitations as a standard. The goal is to establish a laboratory that would standardize and harmonize serological assays for Human Papillomavirus (HPV) antibody testing through development of validated reagents and standards that will be available to the scientific community. The laboratory will provide well qualified and standardized high-throughput testing that adheres to regulatory requirements defined for vaccine development and implementation. The laboratory will work with the scientific community and regulatory entities to identify unmet needs in HPV serology.