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

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, bindin...

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Main 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
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01106-z
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author 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
author_facet 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
author_sort Jinpan Hu
collection DOAJ
description 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.
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spelling doaj-art-b1ae507f91bf4ebfacd0717e5cec922c2025-08-20T02:32:00ZengNature Portfolionpj Vaccines2059-01052025-03-0110111110.1038/s41541-025-01106-zEstablishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency testsJinpan Hu0Zijing Jia1Meng Wang2Lingling Nie3Wangjun Fu4Qingfeng Zhang5Haiyang Qin6Jianhui Nie7Xiaoyu Xu8Lingjie Xu9Fengze Wang10Yingping Chen11Bo Xing12Tao Li13Danfeng Li14Shaowei Li15Ningshao Xia16Xiangxi Wang17Weijin Huang18National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen UniversityCAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesDivision of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesDivision of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)Division of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)Vazyme Biotech Co. LtdVazyme Biotech Co. LtdVazyme Biotech Co. LtdDepartment of Immunization Program, Zhejiang Provincial Center for Disease Control and PreventionDepartment of Immunization Program, Zhejiang Provincial Center for Disease Control and PreventionDivision of HIV/AIDS and Sexually Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)Guangxi Institute for Drug ControlNational Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen UniversityNational Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen UniversityCAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of SciencesNational Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Public Health, Xiamen UniversityAbstract 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.https://doi.org/10.1038/s41541-025-01106-z
spellingShingle 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
Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
npj Vaccines
title Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
title_full Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
title_fullStr Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
title_full_unstemmed Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
title_short Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests
title_sort establishing a universal ivrp method for quadrivalent hpv vaccines to replace in vivo potency tests
url https://doi.org/10.1038/s41541-025-01106-z
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