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A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine

In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experim...

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Autores principales: Zhang, Chao, Zhang, Xueyang, Dai, Wenlong, Liu, Qingwei, Xiong, Pei, Wang, Shuxia, Geng, Lanlan, Gong, Sitang, Huang, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850365/
https://www.ncbi.nlm.nih.gov/pubmed/29385753
http://dx.doi.org/10.3390/v10020058
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author Zhang, Chao
Zhang, Xueyang
Dai, Wenlong
Liu, Qingwei
Xiong, Pei
Wang, Shuxia
Geng, Lanlan
Gong, Sitang
Huang, Zhong
author_facet Zhang, Chao
Zhang, Xueyang
Dai, Wenlong
Liu, Qingwei
Xiong, Pei
Wang, Shuxia
Geng, Lanlan
Gong, Sitang
Huang, Zhong
author_sort Zhang, Chao
collection PubMed
description In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.
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spelling pubmed-58503652018-03-16 A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine Zhang, Chao Zhang, Xueyang Dai, Wenlong Liu, Qingwei Xiong, Pei Wang, Shuxia Geng, Lanlan Gong, Sitang Huang, Zhong Viruses Article In recent years, enterovirus D68 (EVD68) has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM) in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR) suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines. MDPI 2018-01-30 /pmc/articles/PMC5850365/ /pubmed/29385753 http://dx.doi.org/10.3390/v10020058 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Chao
Zhang, Xueyang
Dai, Wenlong
Liu, Qingwei
Xiong, Pei
Wang, Shuxia
Geng, Lanlan
Gong, Sitang
Huang, Zhong
A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title_full A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title_fullStr A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title_full_unstemmed A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title_short A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine
title_sort mouse model of enterovirus d68 infection for assessment of the efficacy of inactivated vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850365/
https://www.ncbi.nlm.nih.gov/pubmed/29385753
http://dx.doi.org/10.3390/v10020058
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