Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus

Japanese encephalitis (JE) is a very severe disease characterized by high fatality rates and the development of permanent behavioral, psychiatric, and neurological sequelae among survivors. Japanese encephalitis virus (JEV), a flavivirus, is responsible for JE. In Asia, Genotype I (GI) has emerged a...

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Main Authors: Eunji Lee, Minjee Kim, Young Bong Kim
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/11/12/1827
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author Eunji Lee
Minjee Kim
Young Bong Kim
author_facet Eunji Lee
Minjee Kim
Young Bong Kim
author_sort Eunji Lee
collection DOAJ
description Japanese encephalitis (JE) is a very severe disease characterized by high fatality rates and the development of permanent behavioral, psychiatric, and neurological sequelae among survivors. Japanese encephalitis virus (JEV), a flavivirus, is responsible for JE. In Asia, Genotype I (GI) has emerged as the dominant strain, replacing Genotype III (GIII). However, no clinically approved drug is available to treat JEV infection, and currently available commercial vaccines derived from JEV GIII strains provide only partial protection against GI. Utilizing a reverse genetics system, this study attempted to produce a novel chimeric JEV strain with high efficacy against JEV GI. Accordingly, a GI/GIII intertypic recombinant strain, namely SA14-GI env, was generated by substituting the E region of the GIII SA14-14-2 strain with that of the GI strain, K05GS. The neurovirulence of the mutant virus was significantly reduced in mice. Analysis of the immunogenicity of the chimeric virus revealed that it induced neutralizing antibodies against JEV GI in mice, and the protective efficacy of SA14-GI env was higher than that of SA14-14-2. These findings suggest that SA14-GI env may be a safe and effective live-attenuated vaccine candidate against JEV GI.
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spelling doaj.art-456230e958894179b2fc1c9335e20b9d2023-12-22T14:47:22ZengMDPI AGVaccines2076-393X2023-12-011112182710.3390/vaccines11121827Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis VirusEunji Lee0Minjee Kim1Young Bong Kim2Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of KoreaDepartment of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of KoreaJapanese encephalitis (JE) is a very severe disease characterized by high fatality rates and the development of permanent behavioral, psychiatric, and neurological sequelae among survivors. Japanese encephalitis virus (JEV), a flavivirus, is responsible for JE. In Asia, Genotype I (GI) has emerged as the dominant strain, replacing Genotype III (GIII). However, no clinically approved drug is available to treat JEV infection, and currently available commercial vaccines derived from JEV GIII strains provide only partial protection against GI. Utilizing a reverse genetics system, this study attempted to produce a novel chimeric JEV strain with high efficacy against JEV GI. Accordingly, a GI/GIII intertypic recombinant strain, namely SA14-GI env, was generated by substituting the E region of the GIII SA14-14-2 strain with that of the GI strain, K05GS. The neurovirulence of the mutant virus was significantly reduced in mice. Analysis of the immunogenicity of the chimeric virus revealed that it induced neutralizing antibodies against JEV GI in mice, and the protective efficacy of SA14-GI env was higher than that of SA14-14-2. These findings suggest that SA14-GI env may be a safe and effective live-attenuated vaccine candidate against JEV GI.https://www.mdpi.com/2076-393X/11/12/1827Japanese encephalitis virusvaccinationreverse genetics system
spellingShingle Eunji Lee
Minjee Kim
Young Bong Kim
Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
Vaccines
Japanese encephalitis virus
vaccination
reverse genetics system
title Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
title_full Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
title_fullStr Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
title_full_unstemmed Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
title_short Attenuated Chimeric GI/GIII Vaccine Candidate against Japanese Encephalitis Virus
title_sort attenuated chimeric gi giii vaccine candidate against japanese encephalitis virus
topic Japanese encephalitis virus
vaccination
reverse genetics system
url https://www.mdpi.com/2076-393X/11/12/1827
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