Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine

Background/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cel...

Full description

Saved in:
Bibliographic Details
Main Authors: Fan Gao, Lingjie Xu, Qian Wang, Gang Wang, Mingchen Liu, Lu Li, Qian He, Xuanxuan Zhang, Ying Wang, Qunying Mao, Zhenglun Liang, Tao Wang, Xiao Ma, Xing Wu
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/13/3/320
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849340282960609280
author Fan Gao
Lingjie Xu
Qian Wang
Gang Wang
Mingchen Liu
Lu Li
Qian He
Xuanxuan Zhang
Ying Wang
Qunying Mao
Zhenglun Liang
Tao Wang
Xiao Ma
Xing Wu
author_facet Fan Gao
Lingjie Xu
Qian Wang
Gang Wang
Mingchen Liu
Lu Li
Qian He
Xuanxuan Zhang
Ying Wang
Qunying Mao
Zhenglun Liang
Tao Wang
Xiao Ma
Xing Wu
author_sort Fan Gao
collection DOAJ
description Background/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cell-based neutralization assay (CBNA), the gold standard for detecting neutralizing antibodies (NtAbs), which are used as indicators of HFMD vaccine efficacy, has several limitations. We aimed to develop a novel assay for detecting NtAbs against a quadrivalent HFMD vaccine. Methods: We developed a four-color pseudovirus-based neutralization assay (PBNA), utilizing fluorescent reporter genes, to rapidly evaluate neutralizing antibodies against EV71, CA16, CA10, and CA6 in multivalent vaccines and compared it with CBNA. Results: PBNA could rapidly and simultaneously detect NtAbs against the four serotypes and required lesser amounts of sera compared to CBNA. A good consistency in determining NtAb titers was observed for PBNA and CBNA. Conclusions: PBNA provides a robust tool for evaluating the efficacy of multivalent HFMD vaccines and conducting seroepidemiological studies.
format Article
id doaj-art-e00c2a542e484b49b5691edd2556c81b
institution Kabale University
issn 2076-393X
language English
publishDate 2025-03-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj-art-e00c2a542e484b49b5691edd2556c81b2025-08-20T03:43:57ZengMDPI AGVaccines2076-393X2025-03-0113332010.3390/vaccines13030320Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease VaccineFan Gao0Lingjie Xu1Qian Wang2Gang Wang3Mingchen Liu4Lu Li5Qian He6Xuanxuan Zhang7Ying Wang8Qunying Mao9Zhenglun Liang10Tao Wang11Xiao Ma12Xing Wu13School of Life Sciences, Tianjin University, Tianjin 300072, ChinaVazyme Biotech Co., Ltd., Nanjing 210089, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaVazyme Biotech Co., Ltd., Nanjing 210089, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaSchool of Life Sciences, Tianjin University, Tianjin 300072, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaNHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, State Key Laboratory of Drug Regulatory Science, Research Units of Innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National Institutes for Food and Drug Control, Beijing 102629, ChinaBackground/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cell-based neutralization assay (CBNA), the gold standard for detecting neutralizing antibodies (NtAbs), which are used as indicators of HFMD vaccine efficacy, has several limitations. We aimed to develop a novel assay for detecting NtAbs against a quadrivalent HFMD vaccine. Methods: We developed a four-color pseudovirus-based neutralization assay (PBNA), utilizing fluorescent reporter genes, to rapidly evaluate neutralizing antibodies against EV71, CA16, CA10, and CA6 in multivalent vaccines and compared it with CBNA. Results: PBNA could rapidly and simultaneously detect NtAbs against the four serotypes and required lesser amounts of sera compared to CBNA. A good consistency in determining NtAb titers was observed for PBNA and CBNA. Conclusions: PBNA provides a robust tool for evaluating the efficacy of multivalent HFMD vaccines and conducting seroepidemiological studies.https://www.mdpi.com/2076-393X/13/3/320hand, foot, and mouth diseaseenterovirusquadrivalent vaccinepseudovirus-based neutralization assay
spellingShingle Fan Gao
Lingjie Xu
Qian Wang
Gang Wang
Mingchen Liu
Lu Li
Qian He
Xuanxuan Zhang
Ying Wang
Qunying Mao
Zhenglun Liang
Tao Wang
Xiao Ma
Xing Wu
Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
Vaccines
hand, foot, and mouth disease
enterovirus
quadrivalent vaccine
pseudovirus-based neutralization assay
title Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
title_full Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
title_fullStr Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
title_full_unstemmed Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
title_short Four-Color Pseudovirus-Based Neutralization Assay: A Rapid Method for Evaluating Neutralizing Antibodies Against Quadrivalent Hand, Foot, and Mouth Disease Vaccine
title_sort four color pseudovirus based neutralization assay a rapid method for evaluating neutralizing antibodies against quadrivalent hand foot and mouth disease vaccine
topic hand, foot, and mouth disease
enterovirus
quadrivalent vaccine
pseudovirus-based neutralization assay
url https://www.mdpi.com/2076-393X/13/3/320
work_keys_str_mv AT fangao fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT lingjiexu fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT qianwang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT gangwang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT mingchenliu fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT luli fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT qianhe fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT xuanxuanzhang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT yingwang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT qunyingmao fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT zhenglunliang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT taowang fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT xiaoma fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine
AT xingwu fourcolorpseudovirusbasedneutralizationassayarapidmethodforevaluatingneutralizingantibodiesagainstquadrivalenthandfootandmouthdiseasevaccine