Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in re...

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Main Authors: Kaihao Feng, Xiaoyan Zheng, Ran Wang, Na Gao, Dongying Fan, Ziyang Sheng, Hongning Zhou, Hui Chen, Jing An
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcimb.2020.00087/full
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author Kaihao Feng
Xiaoyan Zheng
Ran Wang
Na Gao
Dongying Fan
Ziyang Sheng
Hongning Zhou
Hui Chen
Jing An
Jing An
author_facet Kaihao Feng
Xiaoyan Zheng
Ran Wang
Na Gao
Dongying Fan
Ziyang Sheng
Hongning Zhou
Hui Chen
Jing An
Jing An
author_sort Kaihao Feng
collection DOAJ
description Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 μg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.
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spelling doaj.art-29d7cb6f6d1b4b9282a9da6f426733332022-12-22T03:40:22ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-03-011010.3389/fcimb.2020.00087518051Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in MiceKaihao Feng0Xiaoyan Zheng1Ran Wang2Na Gao3Dongying Fan4Ziyang Sheng5Hongning Zhou6Hui Chen7Jing An8Jing An9Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaBeijing Tropical Medicine Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaYunnan Provincial Key Laboratory of Vector-borne Disease Control and Research, Yunnan Institute of Parasitic Diseases, Pu'er, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaCenter of Epilepsy, Beijing Institute for Brain Disorders, Beijing, ChinaDengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 μg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.https://www.frontiersin.org/article/10.3389/fcimb.2020.00087/fulldengue virusDNA vaccineprM-Eimmunizationcross-protection
spellingShingle Kaihao Feng
Xiaoyan Zheng
Ran Wang
Na Gao
Dongying Fan
Ziyang Sheng
Hongning Zhou
Hui Chen
Jing An
Jing An
Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
Frontiers in Cellular and Infection Microbiology
dengue virus
DNA vaccine
prM-E
immunization
cross-protection
title Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
title_full Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
title_fullStr Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
title_full_unstemmed Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
title_short Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice
title_sort long term protection elicited by a dna vaccine candidate expressing the prm e antigen of dengue virus serotype 3 in mice
topic dengue virus
DNA vaccine
prM-E
immunization
cross-protection
url https://www.frontiersin.org/article/10.3389/fcimb.2020.00087/full
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