An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice

Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like p...

Full description

Bibliographic Details
Main Authors: Xin Liu, Hanyu Zhu, Mei Wang, Ning Zhang, Jing Wang, Wenbian Tan, Guochuan Wu, Pei Yu, Hongbo Liu, Qiliang Liu
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Virus Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0168170223001971
_version_ 1797659912242724864
author Xin Liu
Hanyu Zhu
Mei Wang
Ning Zhang
Jing Wang
Wenbian Tan
Guochuan Wu
Pei Yu
Hongbo Liu
Qiliang Liu
author_facet Xin Liu
Hanyu Zhu
Mei Wang
Ning Zhang
Jing Wang
Wenbian Tan
Guochuan Wu
Pei Yu
Hongbo Liu
Qiliang Liu
author_sort Xin Liu
collection DOAJ
description Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like particle of EV-A71 (EV-A71-VLPCHI3) was constructed based on EV-A71-VLP backbone by replacing the corresponding surface loops with CV-A16 VP1 G-H, CV-A10 VP1 B-C and E-F loops, which are critical for immunogenic neutralization. The baculovirus-insect cell expression system was employed for EV-A71-VLPCHI3 production. EV-A71-VLPCHI3 was purified by sucrose density gradient and observed by transmission electron microscopy. The immunogenicity and protective efficacy of EV-A71-VLPCHI3 were evaluated in mice. Our results revealed that EV-A71-VLPCHI3 had a similar morphology to inactivated EV-A71 particles and could induce specific IgG antibodies against EV-A71, CV-A16 and CV-A10 in mice. More importantly, EV-A71-VLPCHI3 enhanced cross-reactive protection against CV-A16 and CV-A10, by 20 % and 40 %, compared to inactivated EV-A71 counterparts, respectively. In conclusion, the successful construction of EV-A71-VLPCHI3 suggested that loop-dependent heterologous protection could be transferred by loops replacement on the surface of viral capsid. This strategy may also supplement the development of multivalent vaccines against other infectious viral diseases.
first_indexed 2024-03-11T18:22:06Z
format Article
id doaj.art-64a3abe1b21b4a0284ef96f69d176322
institution Directory Open Access Journal
issn 1872-7492
language English
last_indexed 2024-03-11T18:22:06Z
publishDate 2023-11-01
publisher Elsevier
record_format Article
series Virus Research
spelling doaj.art-64a3abe1b21b4a0284ef96f69d1763222023-10-15T04:36:37ZengElsevierVirus Research1872-74922023-11-01337199235An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in miceXin Liu0Hanyu Zhu1Mei Wang2Ning Zhang3Jing Wang4Wenbian Tan5Guochuan Wu6Pei Yu7Hongbo Liu8Qiliang Liu9Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; College of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; College of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, ChinaCollege of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, ChinaCollege of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, ChinaCollege of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, ChinaClinical Laboratory Medicine Department, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, ChinaDepartment of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; Corresponding authors at: Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China.Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China; College of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China; Key Laboratory of Medical Biotechnology and Translational Medicine, Education Department of Guangxi Zhuang Autonomous Region, Guilin, Guangxi 541100, China; Corresponding authors at: Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China.Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like particle of EV-A71 (EV-A71-VLPCHI3) was constructed based on EV-A71-VLP backbone by replacing the corresponding surface loops with CV-A16 VP1 G-H, CV-A10 VP1 B-C and E-F loops, which are critical for immunogenic neutralization. The baculovirus-insect cell expression system was employed for EV-A71-VLPCHI3 production. EV-A71-VLPCHI3 was purified by sucrose density gradient and observed by transmission electron microscopy. The immunogenicity and protective efficacy of EV-A71-VLPCHI3 were evaluated in mice. Our results revealed that EV-A71-VLPCHI3 had a similar morphology to inactivated EV-A71 particles and could induce specific IgG antibodies against EV-A71, CV-A16 and CV-A10 in mice. More importantly, EV-A71-VLPCHI3 enhanced cross-reactive protection against CV-A16 and CV-A10, by 20 % and 40 %, compared to inactivated EV-A71 counterparts, respectively. In conclusion, the successful construction of EV-A71-VLPCHI3 suggested that loop-dependent heterologous protection could be transferred by loops replacement on the surface of viral capsid. This strategy may also supplement the development of multivalent vaccines against other infectious viral diseases.http://www.sciencedirect.com/science/article/pii/S0168170223001971Hand-foot-and-mouth diseaseEnterovirusVirus-like particleChimeric vaccine
spellingShingle Xin Liu
Hanyu Zhu
Mei Wang
Ning Zhang
Jing Wang
Wenbian Tan
Guochuan Wu
Pei Yu
Hongbo Liu
Qiliang Liu
An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
Virus Research
Hand-foot-and-mouth disease
Enterovirus
Virus-like particle
Chimeric vaccine
title An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
title_full An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
title_fullStr An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
title_full_unstemmed An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
title_short An enterovirus A71 virus-like particle with replaced loops confers partial cross-protection in mice
title_sort enterovirus a71 virus like particle with replaced loops confers partial cross protection in mice
topic Hand-foot-and-mouth disease
Enterovirus
Virus-like particle
Chimeric vaccine
url http://www.sciencedirect.com/science/article/pii/S0168170223001971
work_keys_str_mv AT xinliu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT hanyuzhu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT meiwang anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT ningzhang anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT jingwang anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT wenbiantan anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT guochuanwu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT peiyu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT hongboliu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT qiliangliu anenterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT xinliu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT hanyuzhu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT meiwang enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT ningzhang enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT jingwang enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT wenbiantan enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT guochuanwu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT peiyu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT hongboliu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice
AT qiliangliu enterovirusa71viruslikeparticlewithreplacedloopsconferspartialcrossprotectioninmice