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Viruses 2018, 10(2), 58; https://doi.org/10.3390/v10020058

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

1
Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, China
2
Unit of Vaccinology & Antiviral Strategies, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 16 January 2018 / Revised: 27 January 2018 / Accepted: 29 January 2018 / Published: 30 January 2018
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

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. View Full-Text
Keywords: enterovirus D68; acute flaccid myelitis; mouse model; inactivated vaccine; neutralizing antibody enterovirus D68; acute flaccid myelitis; mouse model; inactivated vaccine; neutralizing antibody
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Zhang, C.; Zhang, X.; Dai, W.; Liu, Q.; Xiong, P.; Wang, S.; Geng, L.; Gong, S.; Huang, Z. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine. Viruses 2018, 10, 58.

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