Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests.

IF 6.9 1区医学 Q1 IMMUNOLOGY

NPJ Vaccines Pub Date : 2025-03-22 DOI:10.1038/s41541-025-01106-z

Jinpan Hu, Zijing Jia, Meng Wang, Lingling Nie, Wangjun Fu, Qingfeng Zhang, Haiyang Qin, Jianhui Nie, Xiaoyu Xu, Lingjie Xu, Fengze Wang, Yingping Chen, Bo Xing, Tao Li, Danfeng Li, Shaowei Li, Ningshao Xia, Xiangxi Wang, Weijin Huang

{"title":"Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests.","authors":"Jinpan Hu, Zijing Jia, Meng Wang, Lingling Nie, Wangjun Fu, Qingfeng Zhang, Haiyang Qin, Jianhui Nie, Xiaoyu Xu, Lingjie Xu, Fengze Wang, Yingping Chen, Bo Xing, Tao Li, Danfeng Li, Shaowei Li, Ningshao Xia, Xiangxi Wang, Weijin Huang","doi":"10.1038/s41541-025-01106-z","DOIUrl":null,"url":null,"abstract":"<p><p>Several human papillomavirus (HPV) L1-based virus-like particle (VLP) vaccines are in development to meet future global vaccination needs. Type-specific monoclonal antibodies with good reactivity to all types of vaccines are urgently needed to evaluate vaccine potency. In this study, binding activity, neutralizing activity, conformational sensitivity, immunodominance in human serum, and versatility were compared among antibodies. A broad-spectrum binding antibody (C4-F5-127) was selected as the capture antibody; four type-specific neutralizing antibodies (6-F5-77, 11-F5-187, 16-F5-196, and 18-F5-203) were selected as detection antibodies for HPV6, 11, 16, and 18, respectively. These antibodies formed a standardized and universal in vitro relative potency (IVRP) assay kit. High-resolution cryo-electron microscopy (cryo-EM) structures of HPV6-6-F5-77, HPV11-11-F5-187, HPV16-16-F5-196 and HPV18-18-F5-203 complexes define the location and nature of epitopes, revealing serotype specific binding modes and neutralization mechanisms. The IVRP results were correlated with potency data from mouse models, offering an efficient alternative to in vivo potency experiments.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"55"},"PeriodicalIF":6.9000,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928608/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Vaccines","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41541-025-01106-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Several human papillomavirus (HPV) L1-based virus-like particle (VLP) vaccines are in development to meet future global vaccination needs. Type-specific monoclonal antibodies with good reactivity to all types of vaccines are urgently needed to evaluate vaccine potency. In this study, binding activity, neutralizing activity, conformational sensitivity, immunodominance in human serum, and versatility were compared among antibodies. A broad-spectrum binding antibody (C4-F5-127) was selected as the capture antibody; four type-specific neutralizing antibodies (6-F5-77, 11-F5-187, 16-F5-196, and 18-F5-203) were selected as detection antibodies for HPV6, 11, 16, and 18, respectively. These antibodies formed a standardized and universal in vitro relative potency (IVRP) assay kit. High-resolution cryo-electron microscopy (cryo-EM) structures of HPV6-6-F5-77, HPV11-11-F5-187, HPV16-16-F5-196 and HPV18-18-F5-203 complexes define the location and nature of epitopes, revealing serotype specific binding modes and neutralization mechanisms. The IVRP results were correlated with potency data from mouse models, offering an efficient alternative to in vivo potency experiments.

查看原文本刊更多论文

为四价人类乳头瘤病毒疫苗建立通用的 IVRP 方法，以取代体内效力测试。

为了满足未来全球疫苗接种的需要，目前正在开发几种基于人乳头瘤病毒（HPV）L1 病毒样颗粒 (VLP) 的疫苗。目前迫切需要对所有类型疫苗都具有良好反应性的特异性单克隆抗体来评估疫苗的效力。本研究比较了不同抗体的结合活性、中和活性、构象敏感性、人血清中的免疫优势和多功能性。研究选择了一种广谱结合抗体（C4-F5-127）作为捕获抗体；选择了四种特异性中和抗体（6-F5-77、11-F5-187、16-F5-196 和 18-F5-203）作为检测抗体，分别检测 HPV6、11、16 和 18。这些抗体组成了一个标准化的通用体外相对效力（IVRP）检测试剂盒。HPV6-6-F5-77、HPV11-11-F5-187、HPV16-16-F5-196 和 HPV18-18-F5-203 复合物的高分辨率冷冻电镜（cryo-EM）结构确定了表位的位置和性质，揭示了血清型特异性结合模式和中和机制。IVRP 的结果与小鼠模型的效力数据相关联，为体内效力实验提供了一种有效的替代方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NPJ Vaccines Immunology and Microbiology-Immunology

CiteScore

11.90

自引率

4.30%

发文量

146

审稿时长

11 weeks

期刊介绍： Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.