【前沿速递】重磅!我国科学家成功建立可评估所有HPV疫苗效价的通用方法

近日,中国食品药品检定研究院王佑春教授团队和厦门大学分子疫苗学与分子诊断学国家重点实验室李少伟教授团队研究发现了一种具有有效中和,高亲和力,免疫优势和广泛保护表位的兔单克隆抗体---H16.001,并揭示了其结构表征。该抗体与HPV16衣壳蛋白的结合方式可有助于用于体外评估来自不同的表达系统的所有HPV疫苗。相关研究结果发表于在国际知名期刊《npj Vaccines》杂志。

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随着越来越多的HPV病毒样颗粒(VLP)疫苗的上市,目前,迫切需要一种具有较好反应性的单克隆抗体(mAb)对不同表达系统和生物过程的疫苗进行效价测定。效价测定是HPV疫苗质量控制和批量放行中最关键的项目之一。为了寻找一种最佳的抗体,该研究团队对抗HPV16 L1 VLPs的单克隆抗体进行了多种免疫试验。研究团队发现兔源性单克隆抗体H16.001具有强大的中和活性,对表面血浆共振(SPR)的高亲和力以及对不同来源的VLP的可比反应性,是评估VLP疫苗产品表位完整性和抗原性的最佳候选。同时,该实验室还建立了HPV16假病毒(PsV)与H16.001复合物模型,证明了IVRP分析的独特结合偏好。

为建立一种通用的基于mAb的HPV16疫苗鉴定方法,首先测量了13株HPV16单克隆抗体(H16.001、H16.25F12、H16.26H7、H16.4G12、H16.V5、H16.8A9、H16.17B10、H16.6C7、H16.22G5、H16.25H8、H16.20G3、H16.1D12、,和H16.5C10),最终发现H16.001具有最有效的中和活性,且比知名mAb H16.V5高18倍。 同时,对4种具有代表性的单克隆抗体(H16.001,H16.8A9、H16.V5和H16.4G12),进行SPR分析,发现H16.001对HPV16-L1五聚体的亲和力最高。

H16-001 cryo-EM分析了HPV-001免疫复合物的结构表征(Fig5,Fig6),发现了一种独特的抗体结合模式:H16.001Fab可以参与HPV的六价和五价capsomer(H16.V5Fab优先结合六价capsomer和H16.U4Fab优先结合与五价capsomer)。这种独特的绑定模式可能是与其高效的中和活性相关

(Fig5. Cryo-EM structure reconstruction of HPV16 in complex with FabH16.001.)

(Fig6. Subparticlereconstruction and interaction analysis of HPV16:001 immune complex)

中国食品药品检定研究院黄维金博士、厦门大学何茂洲博士和北京友谊医院的宁婷婷博士为本文的共同第一作者。

附文献信息:

题目:Structural characterization of a neutralizing mAb H16.001,a potentcandidate for a common potency assay for various HPV16 VLPs

DOI:10.1038/s41541-020-00236-w

Abstract:With more human papillomavirus (HPV) virus-like particle (VLP) vaccines to hit the market in future, a monoclonal antibody (mAb) with preferably comparable reactivity against vaccines from different expression systems and bioprocesses is urgently needed for the potency characterization. Among all mAbs against HPV16 collected, rabbit mAb H16.001 is potently neutralizing with the highest affinity, recognizes an immune-dominant epitope, and can comparably react with HPV16 vaccines from various sources. Cryo-electron microscopic (cryo-EM) structure demonstrated that 360 H16.001 Fabs could bind to HPV16 capsid in preferable binding manner without steric hindrance between neighboring Fabs, potentially supporting its identification for VLP structural integrity and utility in monitoring VLP structural probity. This structural analysis indicated that mAb H16.001 afforded unbiased potency characterization for various HPV16 vaccines and was potential for use in vaccine regulation practice. This study also showed a model process for selecting suitable mAbs for potency assays of other vaccines.

本期编辑:Lisa

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