Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus

BACKGROUND: The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported. METHODS/PRINCIPAL FINDINGS: Using in vitro and in vivo tests, bio...

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Autores principales: Cao, Lei, Fu, Shihong, Gao, Xiaoyan, Li, Minghua, Cui, Shiheng, Li, Xiaolong, Cao, Yuxi, Lei, Wenwen, Lu, Zhi, He, Ying, Wang, Huanyu, Yan, Jinghua, Gao, George Fu, Liang, Guodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854478/
https://www.ncbi.nlm.nih.gov/pubmed/27139722
http://dx.doi.org/10.1371/journal.pntd.0004686
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author Cao, Lei
Fu, Shihong
Gao, Xiaoyan
Li, Minghua
Cui, Shiheng
Li, Xiaolong
Cao, Yuxi
Lei, Wenwen
Lu, Zhi
He, Ying
Wang, Huanyu
Yan, Jinghua
Gao, George Fu
Liang, Guodong
author_facet Cao, Lei
Fu, Shihong
Gao, Xiaoyan
Li, Minghua
Cui, Shiheng
Li, Xiaolong
Cao, Yuxi
Lei, Wenwen
Lu, Zhi
He, Ying
Wang, Huanyu
Yan, Jinghua
Gao, George Fu
Liang, Guodong
author_sort Cao, Lei
collection PubMed
description BACKGROUND: The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported. METHODS/PRINCIPAL FINDINGS: Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT(90) method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults. CONCLUSIONS/SIGNIFICANCE: Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.
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spelling pubmed-48544782016-05-07 Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus Cao, Lei Fu, Shihong Gao, Xiaoyan Li, Minghua Cui, Shiheng Li, Xiaolong Cao, Yuxi Lei, Wenwen Lu, Zhi He, Ying Wang, Huanyu Yan, Jinghua Gao, George Fu Liang, Guodong PLoS Negl Trop Dis Research Article BACKGROUND: The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1–G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported. METHODS/PRINCIPAL FINDINGS: Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT(90) method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10–1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults. CONCLUSIONS/SIGNIFICANCE: Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV. Public Library of Science 2016-05-03 /pmc/articles/PMC4854478/ /pubmed/27139722 http://dx.doi.org/10.1371/journal.pntd.0004686 Text en © 2016 Cao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cao, Lei
Fu, Shihong
Gao, Xiaoyan
Li, Minghua
Cui, Shiheng
Li, Xiaolong
Cao, Yuxi
Lei, Wenwen
Lu, Zhi
He, Ying
Wang, Huanyu
Yan, Jinghua
Gao, George Fu
Liang, Guodong
Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title_full Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title_fullStr Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title_full_unstemmed Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title_short Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus
title_sort low protective efficacy of the current japanese encephalitis vaccine against the emerging genotype 5 japanese encephalitis virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854478/
https://www.ncbi.nlm.nih.gov/pubmed/27139722
http://dx.doi.org/10.1371/journal.pntd.0004686
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